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Biomedical subjects

A Stejskalová

Publications and source records attributed to A Stejskalová.

At least 19 recordsLinked to original sources
PubMed2002

Mercury intoxication from skin ointment containing mercuric ammonium chloride.

OBJECTIVE: A one-year follow-up was performed of a 21-year-old man with a 16-year history of diabetes mellitus type I, who had been using ointment containing 10% mercuric ammonium chloride (hydrargyrum amidochloratum; HgNH(2)Cl) for eczema for approximately 3 weeks. Tiredness, fasciculations on the extremities and poor control of diabetes appeared after the end of the ointment treatment. Nephrotic syndrome and hypertension were diagnosed 1 month later. Two months after the ointment application the patient was very weak with tremors of the hands, almost unable to walk, and had lost 20 kg of body weight. He had severe neurasthenic symptoms and his behaviour suggested acute psychosis. METHODS: Internal, neurological and neuropsychological examinations were performed. Mercury in urine was determined by flameless atomic absorption spectrometry. RESULTS: The urine mercury level on admission was 252.0 microg/l. He was treated with Dimaval, sodium (2,3)-dimercaptopropane(-1)-sulphonate capsules for 12 days (total dose 6.3 g). The highest urine mercury excretion during antidote treatment was 2336.0 microg/24 h. The patient had proteinuria of up to 11.10 g/24 h, and renal biopsy revealed diffuse membranous glomerulonephritis of the 1st stage without apparent diabetic nephropathy. Similarly, neuropathy did not have typical signs of diabetic neuropathy. His clinical condition started to improve during the first 2 weeks. Further follow-up has shown slow normalisation of renal functions. After 1 year, proteinuria decreased to 0.62 g/24 h and body weight normalised. Neuropsychological and electromyographic findings became almost normal. CONCLUSION: Severe intoxication developed after a short period of ointment application. Most signs of damage disappeared in the course of 1 year, except mild proteinuria and neuropathy. The evolution was favourable and confirmed the primary role of mercury intoxication in the severe deterioration of the clinical status of the patient.

Administration, Topical↗
PubMed2002

An association of BMI with A (-6) G, M235T and T174M polymorphisms in angiotensinogen gene in essential hypertension.

The aim of the study was to assess the existence of possible associations among frequent polymorphisms in angiotensinogen genes and some of the risk factors for essential hypertension, especially body mass index (BMI) and smoking. A total of 192 control subjects (aged 45.87 +/- 3.0 years) and 206 patients with the essential hypertension (aged 48.71 +/- 8.42 years) were compared at three angiotensinogen gene polymorphisms by considering BMI and smoking status. No significant differences in genotype and/or allelic distribution for either A (-6) G ATG, M235T or T174M polymorphisms between the hypertensive and control groups were proved. Significantly more hypertensives than control persons with BMI above 25 kg/m(2) were observed (P(corr) = 0.009), independently on sex distribution. A percentage of 44.6% of smokers in the control group vs 46.0% of smokers in the hypertensive groups were found. No significant difference in concurrence of BMI above 25 kg/m(2) and positive smoking status between control and hypertensive subjects was found. Statistically significant differences were found between control and hypertensive subjects when compared distributions of subjects with certain genotypes of the three examined polymorphisms considering BMI (P(corr) = 0.0002 for AA+AG of A (-6) G ATG, P(corr) = 0.01 for CC + CT of T(174)M ATG and P(corr) = 0.01 for MT + TT of M235T ATG). No functional relationship among obesity and the examined polymorphisms in vivo are known. We conclude that a different distribution of BMI could influence the results of analyses of angiotensinogen gene polymorphisms in essential hypertension-control studies.

Alleles↗
PubMed2002

Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma.

BACKGROUND: Asthma is a common multifactorial disease, the aetiology of which is attributable to both environmental and genetic factors. The endothelial nitric oxide synthase (NOS3) gene has been implicated in asthma pathogenesis. OBJECTIVE: This study investigated associations of 27 base-pair tandem repeat polymorphism in intron 4 and the Glu298Asp (G894T) variant of the NOS3 gene with atopic asthma in a Czech population. METHODS: Polymerase chain reaction was used to determine the NOS3 genotypes in subjects with atopic asthma (n = 163) and random controls (n = 209). RESULTS: The NOS3 allele or genotype distributions did not differ significantly between the control and asthma groups. However, the common genotype (bb) of the NOS3 polymorphism in intron 4 was found to be significantly associated with total IgE levels (P = 0.006), specific IgE levels for feathers (P = 0.0002) and a positive skin prick test for hay (P = 0.004). In one atopic patient, we identified an additional 27-bp repeat in the NOS3 gene (NOS3c), which occurred in heterozygous combination with the NOS3b allele (NOS3b/c genotype). In addition, we describe a new polymorphism (A5495G) in the NOS3 gene, which was in almost complete linkage disequilibrium with the NOS3 repeat polymorphism in intron 4. The Glu298Asp variant was not associated with asthma and/or related atopic phenotypes in our study. CONCLUSION: Neither the NOS3 'b' allele nor the NOS3 'b/b' genotype showed any general association with atopic asthma, but they were associated with atopy-related phenotypes. We conclude that the NOS3 gene polymorphisms may act as disease modifiers in atopic asthma phenotype in our population.

Adolescent↗
PubMed2002

Relations among serum ferritin, C282Y and H63D mutations in the HFE gene and type 2 diabetes mellitus in the Czech population.

Aims of the study were: (i) to determine the prevalence of mutations C282Y and H63D in the HFE gene causing hereditary hemochromatosis in patients with type 2 diabetes mellitus and non-diabetics, (ii) to investigate the relationship among HFE genotypes, serum ferritin and glucose intolerance and (iii) to assess possible association of HFE mutations with the susceptibility to develop late diabetic complications in the Czech population. Two approaches were employed - the case-control study comprising diabetics and non-diabetic controls (n = 326) and the cross-sectional study comprising subjects with a previously unknown defect of glucose tolerance (n = 113, oral glucose tolerance test performed in each subject). Allele frequencies of C282Y and H63D did not differ between diabetic and control groups nor among subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes. Ferritin levels significantly differed between diabetic and non-diabetic women (P<1.10 (-3)) and among subjects with NGT, IGT and diabetes (P<0.05). Differences in ferritin levels related to particular genotypes of C282Y and H63D were not detected. Prevalence of diabetes in the first and second quartiles of ferritin distribution differed highly significantly from the prevalence in the third and fourth quartiles in women (P = 0.000037), OR = 3.50 (95% CI, 1.89-6.48). The extent of diabetic late complications did not correlate with ferritin plasma levels.

Adult↗
PubMed2002

[Kidney involvement in light-chain deposition disease].

An overview concerning different types of kidney involvement associated with monoclonal gammapathy (MG) is given, focused on light-chain deposition disease (LCDD). Pathophysiologic basis of LCDD remains in the light-chain tissue deposition (resp. in tissue deposition of immunoglobulin's stable domain). This mechanism is typical for monoclonal immunoglobulin's overproduction as found in MG. Clinical picture of LCDD reflects multiorgan character of disorder, while renal lesions rank among the most frequent, serious and best documented ones. Clinical data referring to a group of six patients, treated in our nephrologic department are presented. Diagnosis of LCDD was established on basis of the renal biopsy finding. Renal functions were decreased at the time of diagnosis in all patients, whereas haemodialysis treatment was started in one patient. On conclusion therapeutic possibilities of LCDD are discussed, in which number symptomatic therapy of renal failure is combined with corticosteroids therapy and cytostatic therapy; prognosis of most patients remains serious.

Aged↗
PubMed2002

[Renal infiltration in lymphoma--diagnosis in renal biopsy (case report)].

A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB in patient with known malignancy and onset of renal failure was indicated with regard to an atypical picture of kidney involvement (non-enlarged kidneys, without any structural changes typical for tumour mass presence). Though spread of the primary tumour to the kidney is not uncommon, involvement severe enough to impair renal function is unusual and occurs primarily with rapidly growing haematologic malignancies; diagnosis is being established by renal biopsy only rarely.

Aged↗
PubMed2001

Polymorphisms 1704G/T and 2184A/G in the RAGE gene are associated with antioxidant status.

The formation of advanced glycation end products (AGEs) and oxidative stress are supposed to play an important role in the development of diabetic late complications. AGEs can bind to several binding sites including receptor of advanced glycation end products (RAGE). AGE-RAGE interaction results in free radical generation. The aim of the present study was to investigate the impact of previously described polymorphisms in the RAGE gene (G82S, 1704G/T, 2184A/G, and 2245G/A) on the glycoxidation status in non-insulin-dependent diabetes mellitus (NIDDM). A total of 371 unrelated caucasian subjects were enrolled in the study. The NIDDM group consisted of 202 subjects, and the presence of late diabetic complications in 5 particular localizations was expressed as an index (I(compl)). The nondiabetic group included 169 subjects. Glycated hemoglobin (HbA(1c)), glycated stratum corneum proteins (Amadori, AGE), total carotenoids, alpha- and beta -carotene, gamma-tocopherol, lutein, lycopene, and alpha-tocopherol were measured in each subject. Statistically significant differences in allele frequencies between the NIDDM and the nondiabetic groups were observed for the G82S and 2245G/A polymorphisms (P =.047 and .032, respectively). HbA(1c), Amadori, and AGE did not reveal any significant association with any of the polymorphisms analyzed. However, significant differences between subjects bearing "wild-type majority" genotypes 1704GG+2184AA and subjects with "mutated" genotypes were found for total carotenoids (P =.001), alpha-carotene (P =.046), beta-carotene (P =.028), lutein (P =.001), lycopene (P =.006), and alpha-tocopherol (P =.047). I(compl) significantly correlated with the plasma levels of all antioxidants (all P <.01), while no correlation of I(compl) with glycation variables was observed. The newly identified intron polymorphisms in the RAGE gene were proved to be associated with the antioxidant status in NIDDM subjects. The extent of diabetic vascular disease is related to the plasma levels of antioxidants.

Alleles↗
PubMed2001

Transjugular renal biopsy. Our experience with 67 cases.

BACKGROUND: Transjugular renal biopsy (TJRB) is still a novel technique of renal tissue sampling exploiting the transjugular route. TJRB should be performed particularly in situations when the percutaneous route is precluded, i.e. especially in patients with clotting disorders. In the past, only a few papers reported the experience with larger numbers of patients. The goal of this paper is to analyze our experience with TJRB. METHODS AND RESULTS: From 1993 to 1999, 67 patients, mean age 49.8 years (SD +/- 10.2), male/female ratio 40/27, underwent TJRB. Fifty-two patients (78%) suffered from renal insufficiency and 19 of them (28%) were on dialysis treatment at the time of TJRB. Arterial hypertension was recorded in 42%. The combined kidney and liver biopsy (46%) and clotting disorders (39%) were the most frequent indications for performing TJRB. Renal tissue was yielded in 53 patients (79%) but a sample sufficient for histological diagnosis was taken in 49 (73%), reaching on average 10.8 glomeruli. Altogether 19 different histological entities were disclosed and out of them, vascular nephrosclerosis (12%), necrotizing and crescentic glomerulonephritis, IgA nephropathy (IgAN) and amyloidosis (three latter per 10%) represented the most frequent diagnoses. TJRB was combined with liver biopsy in 31 patients (46%) and/or hepatic vein catheterization in 22 patients (33%) confirming portal hypertension in 8. The clinically significant liver histology was found in 20 patients, of them cirrhosis/fibrosis in 8, chronic hepatitis in 4 and steatosis in 5. Among those 20 patients, IgAN was disclosed as the most common renal diagnosis (6). Clinically symptomatic complications were recorded in 12 cases (18%) but 9 of them suffered from clotting disorders. Complications included development of subcapsular hematoma in 6 cases, macroscopic hematuria in 4 cases, and hypovolemic hemorrhagic shock in 2. One patient had to undergo surgical treatment. Dividing the patients into a subgroup with or without clotting disorders, the complication rate was 34 vs. 7%. CONCLUSIONS: TJRB is a new diagnostic method, which, looking at its indications, facilitates the diagnosis of glomerulopathies in patients who could not be considered for percutaneous renal biopsy, particularly due to clotting disorders. The technical aspect of this procedure plays a fundamental role in the final risk/benefit ratio but if done correctly it involves acceptable risk and is well tolerated.

Adult↗
PubMed2000

Long term treatment of IgA nephropathy with cyclosporine A.

20-50% of patients with IgA nephropathy (IgAN) reach end-stage renal failure. Yet a standard treatment for those with progressive course and/or great proteinuria is lacking. We treated 6 patients with biopsy proven IgAN, proteinuria over 3.5 g/24 h and S-creatinine less than 200 micromol/L non-responding to corticosteroids administered for 3 months. They were given cyclosporine A (CsA) 5 mg/kg bw/day then titrated aiming at a serum concentration of 70-150 ng/mL for one year tapered to discontinuation in 9 months. Prednisone 5-10 mg on alternate days was given with CsA. Proteinuria (g/day) decreased from 4.66 +/- 0.43 to 1.38 +/- 0.29 (p < 0.01) after 1 month and to 0.59 +/- 0.14 (p < 0.001) after 1 year of treatment and remained lower than baseline 2 years from the beginning (1.44 +/- 0.27, p < 0.001). GFR (creatinine clearance) did not change during the first month (1.25 +/- 0.21 mL/s vs 1.38 +/- 0.29 mL/s), but decreased after 1 year (1.05 +/- 0.14 mL/s, p < 0.05). After two years it increased to 1.17 +/- 0.16, NS from baseline. We also calculated the ratio of proteinuria to the GFR (mg/L) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80 + 6.47 before therapy, it decreased after 1 month (11.56 +/- 1.7, p < 0.05) and further after 1 year (6.78 + 1.45, p < 0.01). Three months after discontinuation it was still 14.32 +/- 1.00, p < 0.05 from baseline. In conclusion, CsA significantly lowered moderate to high proteinuria in 6 patients with IgAN. Significant decrease of the proteinuria/GFR ratio suggests some non-hemodynamic mechanism of CsA action. The therapy was well tolerated and side-effects were not so severe as to require CsA withdrawal.

Adult↗
PubMed1999

Clinical features and natural history of IgA nephropathy.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. It is characterized by recurrent gross hematuria, microhematuria and/or proteinuria and diffuse mesangial IgA deposits in glomeruli. It is predominantly a disease of young males. Apart from primary IgAN (Berger's disease), IgA deposits in the glomeruli are also seen in Henoch-Schönlein purpura and in association with various of other diseases, particularly liver cirrhosis. Originally it was thought that IgAN was a benign disease, but it is now known that approximately 20-40% of patients develop progressive renal disease 5 to 25 years after diagnosis and progress to end-stage renal disease. Clinical predictors of progressive disease are elevated serum creatinine concentration at presentation, increased systemic blood pressure, persistent protein excretion > 1.0 g/day and histological predictors are glomerulosclerosis, tubular atrophy/interstitial fibrosis, extension of immune deposits to the perivascular space and crescent formation. Progression correlates more closely with the severity of tubulointerstitial lesions than with the degree of glomerular lesions. These features of IgAN reported in literature were mostly, but not completely, confirmed by analysis of all consecutive patients with biopsy proven IgAN and follow-up > 12 months in the renal units of Heidelberg and Prague using univariate analysis, multiple range test and multiple regression analysis.

Adult↗
PubMed1998

[Soluble cytokinin receptors in renal vasculitis and lupus nephritis].

BACKGROUND: Activation of various cytokines, e.g. TNF alpha, IL-1 and/or IL-6 may play important role in the pathogenesis of renal vasculitis and lupus nephritis (LN). Systemic effects of these cytokines may be modulated by their circulating soluble receptors. Plasma levels of cytokine receptors may thus be also markers of the activation of these cytokines. METHODS AND RESULTS: Plasma levels of TNF alpha, its soluble receptor p75 (sTNF-RII), IL-6 and soluble IL-6 receptor (sIL-6R) were measured using ELISA in 17 pts with ANCA-positive renal vasculitis (12 active-ANCA-A, 7 in remission ANCA-R), 9 pts with active lupus nephritis (LN) and 5 healthy subjects. Pts with LN had in comparison with controls increased plasma levels of TNF alpha, sTNF-RII, IL-6 and sIL-6R. Pts with ANCA-A had also in comparison with controls increased plasma levels of TNF alpha, sTNF-RII and sIL-6R, but plasma levels of IL-6 were not significantly increased dut to great standard deviation. Pts with ANCA-R had in comparison with controls increased plasma levels of sTNF-RII, but plasma levels of TNF alpha were in ANCA-R significantly lower than in ANCA-A. While the ratio TNF alpha/sTNF-RII was significantly lower in all groups of pts than in controls, the ratio IL-6R/sIL-6R was in comparison with controls significantly increased only in LN. CONCLUSIONS: While increased plasma levels of TNF alpha may be nonspecific marker of the activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are increased also in pts with ANCA-positive renal vasculitis in remission. Increased plasma levels of sTNF-RII may interfere with systemic effects of TNF alpha, but may also prolong the lifetime of its active form. Plasma levels of sIL-6R are increased both in ANCA-A and in LN, but their increase is, however, much less pronounced than that of sTNF-RII and cannot effectively block systemic effects of IL-6.

Adult↗
PubMed1998

[Laboratory findings and serum levels of amyloid A and soluble interleukin-2 receptors in patients with renal amyloidosis].

BACKGROUND: Renal amyloid involvement results either from primary or secondary amyloidosis. Extent of amyloid tissue deposition in kidneys and clinical course depends not only on the type of basic process but reflects also time of diagnosis and possibility to influence the basic process. METHODS AND RESULTS: We analyzed laboratory and clinical data of patients with bioptically proven renal amyloidosis. We found renal amyloidosis in 27 patients from an overall number of 750 renal biopsies (RB) performed in our department (i.e. 3.6%). AA amyloidosis was diagnosed in 16 pts, AL amyloidosis in 11 pts. About 50% of patients had laboratory signs of nephrotic syndrome, all patients had various degree of proteinuria. Impaired renal function were found in more than 50% of patients, in 6 of them we had to start renal replacement therapy. 8 pts died. Complications of severe nephrotic syndrome were the causes of death in majority of cases. We have started investigation of some amyloid precursors and cytokines in patients with AA and AL amyloidosis. We compared the results with group of patients with vasculitis. We investigated plasma and urinary levels of SAA (serum AA) and soluble receptor for interleukin 2 (sIL-2R). CONCLUSIONS: Clinical features and laboratory findings in our patients with renal amyloidosis approximately are in accordance with literary data. Plasmatic level of SAA was increased not only in the group of patients with AA amyloidosis, but also in the group of vasculitis. Urinary sIL-2R was significantly increased in patients with AA amyloidosis in comparison with healthy controls.

Adult↗
PubMed1998

Cytokines and adhesion molecules in renal vasculitis and lupus nephritis.

BACKGROUND: Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. METHODS: Plasma levels and urinary excretion of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 14 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. RESULTS: Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-alpha (9.27 +/- 3.19% vs 0.58 +/- 0.02%, P < 0.01), IL-6 (120.79 +/- 65.83% vs 1.89 +/- 0.34%, P < 0.01) and increased fractional excretion of IL-8 (23.34 +/- 6.38% vs 2.56 +/- 1.07%, P < 0.01) and sVCAM-1 (0.81 +/- 0.33% vs 0.03 +/- 0.02%, P < 0.01) compared with controls. Urinary excretion of TNF-alpha and IL-6 and fractional excretion of TNFalpha, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-alpha (20.52 +/- 2.01 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05) and sVCAM-1 (1537.88 +/- 276.36 ng/ml vs 692.26 +/- 44.42 ng/ml, P < 0.05) and increased urinary excretion of TNF-alpha (2.81 +/- 0.51 microg/mol creat vs 0.98 +/- 0.05 microg/mol creat, P < 0.01), IL-8 (35.78 +/- 14.03 microg/mol creat vs 12.46 +/- 5.19 microg/mol creat, P < 0.05) and sVCAM-1 (48.98 +/- 20.20 microg/mol creat vs 2.92 +/- 1.35 microg/mol creat, P < 0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-alpha (18.10 +/- 0.57 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05). CONCLUSIONS: Urinary excretion and fractional excretion, but not plasma levels, of selected pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.

Adult↗
PubMed1998

ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats.

BACKGROUND: Reactive oxygen species produced during metabolism of adriamycin are purported to play an important role in the pathogenesis of experimental adriamycin nephropathy in rats. ICRF-187 (dexrazoxan, Cardioxan), an iron chelator, has been shown to inhibit adriamycin-induced formation of hydroxyl radical and to decrease adriamycin cardiotoxicity in oncological patients. The aim of our study was to assess the putative protective role of ICRF-187 in adriamycin nephropathy by evaluating the possible participation of free radicals in its pathogenesis. METHODS: We examined five experimental groups. Group A, received a single dose of adriamycin (5 mg/kg bw i.v.), group CA was given a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration, group CCA received a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration followed by three weekly intraperitoneal injections (100 mg/kg bw) ICRF-187. Group CC received one dose of ICRF-187 (100 mg/kg bw i.v.) followed by three weekly intraperitoneal injections of ICRF-187, and group N served as control receiving saline. Common biochemical parameters, malondialdehyde (MDA) and antioxidant enzymes (glutathione peroxidase--GPx and superoxide dismutase--SOD) in blood and kidney homogenates were measure and histology of the kidney was studied after the rats were sacrificed. RESULTS: Full-blown nephrotic syndrome developed after 3 weeks only in A rats. Nephrotic syndrome was completely prevented in all ICRF-187 treated rats (CA, CCA). Proteinuria was significantly increased in A rats (108.2 + 48.4 mg/l of glomerular filtrate) compared with CA (12.4 + 6.8 mg/l, P < 0.0001) and with N (6.1 + 3.5 mg/l, P < 0.0001). Total MDA in erythrocytes was significantly increased only in A rats (1.7 + 0.3 micromol/l) and was completely normalized by ICRF-187 in CA (1.1 + 0.2 micromol/l, P < 0.001). Total TBARS and MDA in kidney homogenates were significantly elevated in groups with repeated administration of ICRF-187 (CC and CCA rats) compared to N, CA, A groups. Activity of GPx and SOD in kidney homogenate and in erythrocytes was not significantly increased by ICRF-187 in adriamycin treated rats. Histologic changes in A rats resembled minimal change nephropathy with fusion of foot processes and hyaline casts in tubules. There was only minimal mesangial proliferation and perivascular mast cell infiltrates in all groups of ICRF-187-treated rats. CONCLUSIONS: We conclude that ICRF-187, probably by chelation iron, completely protected rats from adriamycin-induced nephrotic syndrome. It supports the role of iron-mediated reactive oxygen species in the development of this type of glomerular injury. However, repeated administration of ICRF-187 alone is able to increase parameters of oxidative stress in the kidney.

Animals↗
PubMed1998

Influence of plasma exchange on serum levels of cytokines and adhesion molecules in ANCA-positive renal vasculitis.

BACKGROUND: Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis not only by removing pathogenic autoantibodies, but also by lowering the serum levels of circulating cytokines. METHODS: Serum levels of IL-1beta, IL-1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA-positive renal vasculitis (5 patients with Wegener's granulomatosis, WG, and 5 patients with microscopic polyangiitis, MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained at the beginning and at the end of the 1st, 3rd and 5th PE and in samples of filtrate obtained during the same PE. RESULTS: In comparison with controls, patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1 before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased in patients with MPA, and the serum levels of all the cytokines and adhesion molecules measured in patients with WG were increased. At the end of the PE course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change in serum levels of IL-1beta and IL-8, and the serum levels of IL-1ra and IL-6 even increased at the end of a single PE, in spite of high levels of all cytokines and adhesion molecules in the plasma filtrate. CONCLUSION: Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by a PE course. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with the synthetic membrane. The insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.

Adult↗
PubMed1998

Effect of 1 year cyclosporine A treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study.

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.

Adult↗
PubMed1997

[The effect of plasmapheresis on cytokine serum levels and adhesion molecules in ANCA-positive renal vasculitis].

BACKGROUND: Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active ANCA-positive renal vasculitis (ANCA-A). Plasma exchange (PE) may influence the activity of vasculitis not only by removal of pathogenic autoantibodies, but also by lowering of serum levels of circulating cytokines. METHODS AND RESULTS: Serum levels of IL-1, IL. 1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 pts with active ANCA-positive renal vasculitis (5 pts with Wegener's granulomatosis-WG, 5 pts with microscopic polyangiitis-MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained in the beginning and at the end of the 1st, 3rd and 5th PE and in the samples of filtrate obtained during the same PE. Pts with ANCA had before the 1st PE in comparison with controls higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1. There were increased serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 in pts with MPA and increased serum levels of all measured cytokines and adhesion molecules in pts with WG. At the end of the course of PE there was the decrease of serum levels of IL-ira and VCAM-1 in pts with ANCA and IL-1ra and ICAM-1 in WG. Single PE led in pts with ANCA only to the decrease of serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change of serum levels of IL-1 and IL-8 serum levels of IL-1ra and IL-6 even increased at the end of single PE, in spite of high levels of all cytokines and adhesion molecules in plasmafiltrate. CONCLUSIONS: Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by the course of PE. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with synthetic membrane. Insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.

Adult↗