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Biomedical subjects

M Jirsa

Publications and source records attributed to M Jirsa.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Effect of losartan and enalapril on urinary excretion of 8-isoprostane in experimental nephrotic syndrome].

BACKGROUND: Increased permeability of glomerular capillary wall in adriamycin nephropathy may be mediated by increased generation of free radicals and possibly also by the non-enzymatic production of isoprostanes induced by oxidative stress. ACE inhibitors may reduce proteinuria, possibly due to the decrease of intraglomerular pressure and increased permselectivity of the glomerular capillary wall. These effects may be partly mediated by the inhibition of the degradation of kinins. It is not clear if newly available angiotensin II antagonists have the same antiproteinuric and renoprotective effects. METHODS AND RESULTS: We compared the effect of an ACE inhibitor (enalapril, 0.4 mg/kg bw i.p. daily for 3 weeks) and angiotensin II antagonist (losartan, 2 mg/kg bw in the same way) on experimental nephrotic syndrome induced in rats by the administration of adriamycin (5 mg/kg bw i.v. in a single dose). To elucidate the potential differences between these two drugs we also measured total malondialdehyde in blood and urinary excretion some eicosanoids and their metabolites (TxB2, 6-keto-PGF1alfa, bicyclo-PGE2 and 8-isoprostane). Proteinuria increased in adriamycin treated rats after 3 weeks from 0.18 +/- 0.01 to 0.44 +/- 0.14 g/mmol creat, p < 0.01. This increase was not prevented by losartan (increase from 0.18 +/- 0.12 to 0.50 +/- 0.11 g/mmol creat, p < 0.05), but tended to be partly blunted by enalapril (increase from 0.20 +/- 0.10 to only 0.32 +/- 0.08 g/mmol creat, p < 0.05). Similarly there was no increase of serum cholesterol, only in enalapril treated rats. On the other hand, both losartan (1.27 +/- 0.13 vs. 1.91 +/- 0.30 mumol/l, p < 0.05) and enalapril (0.93 +/- 0.06 mumol/l, p < 0.001) prevented adriamycin induced increase of total MDA in serum, but urinary excretion of 8-isoprostane was increased in nephrotic rats treated by losartan compared to controls. Enalapril induced increase of urinary excretion of bicyclo-PGE2 (4.32 +/- 0.62 vs. 1.66 +/- 0.81 ng/mmol creat, p < 0.001) was possibly mediated by kinins. There was no significant difference in the urinary excretion of other eicosanoids between different groups, but proteinuria correlated positively with urinary excretion of 8-isoprostane (p < 0.01). Proteinuric rats had also significantly higher urinary excretion of 8-isoprostane than non-proteinuric rats (44.8 +/- 7.1 vs. 26.7 +/- 3.4 ng/mmol. creat, p < 0.05). CONCLUSIONS: Our data suggest that proteinuria in adriamycin nephropathy may mainly depend on free radical generation and the formation of 8-isoprostane. Haemodynamic parameters (glomerular pressure) do not seem to be so important. The mild antiproteinuric effect of enalapril may suggest a contributory role of the inhibition of kinin degradation in this model of nephrotic syndrome.

Angiotensin II↗
PubMed1999

Can serum amyloid A or macrophage colony stimulating factor serve as marker of amyloid formation process?

Amyloid formation depends on amyloid precursor production and is influenced by the activity of the underlying disorder and mediated by some proinflammatory cytokines. In this pilot study we tried to find some specific markers that could establish the activity of the disease. We investigated 45 samples of sera and 38 samples of urine from patients (pts) with secondary amyloidosis (AA), primary amyloidosis (AL), systemic autoimmune diseases with renal impairment (Vasc) and healthy controls (Co). Pts with AA had increased plasma levels of TNF alpha (9.97 +/- 4.22 vs. 2.63 +/- 1.34 pg/mL, p < 0.001) and SAA (43.14 +/- 16.0 vs. 3.42 +/- 0.7 ng/mL, p < 0.05) in comparison with Co. Plasma levels of M-CSF in the AA group were significantly increased in comparison with Co (1077.34 +/- 238.6 vs. 137.71 +/- 19.6, pg/mL, p < 0.001) and also in comparison with Vasc (482.24 +/- 86.7 pg/mL, p < 0.05). Urinary excretions of TNF alpha (8.92 +/- 8.1 vs. 0.17 +/- 0.11 microgram/mol creatinine, p < 0.01), sIL-6R (1.39 +/- 1.14 vs. 0.07 +/- 0.05 g/mol creatinine, p < 0.01) and M-CSF (650.2 +/- 153.7 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in AA were significantly increased in comparison with Co. Pts with AL had increased plasma levels of M-CSF (819.83 +/- 264.2 vs. 137.71 +/- 19.6 pg/mL, p < 0.05) and urinary excretion of M-CSF (865.0 +/- 188.4 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in comparison with Co. SAA has a low specificity for amyloidosis but is a sensitive acute phase reactant. TNF alpha, a proinflammatory cytokine, may reflect the activity of the underlying diseases in secondary amyloidosis. M-CSF was increased both in plasma and urine in amyloidosis groups and seems to be the most promising (possibly specific) marker of amyloidosis.

Amyloid↗
PubMed1998

[Soluble adhesive molecules and cytokines in patients with myasthenia gravis treated with plasmapheresis].

BACKGROUND: Plasma exchange (PE) is effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except from acetylcholine receptor antibodies (AChRAb) some other inflammatory mediators possibly activated in MG may be also removed during PE. METHODS AND RESULTS: Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 patients (pts) with MG indicated to the treatment with PE. Pts were subdivided on the basis of the serum levels of AChRAb into 2 groups (8 pts with low AChRAb, 12 pts with high AChRAb). Soluble adhesion molecules and cytokines were measured before the 1st and last PE, at the end of the 1st PE and in the samples of plasma filtrate obtained during the 1st PE. Pts with MG had before the 1st PE higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both the first PE and the course of PE led to the substantial decrease of serum levels of AChRAb, sICAM-1 and sVCAN-1, serum levels of sIL-2R and sTNF-R II were not, however, significantly influenced by both the single and the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrate, too. Pts with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than pts with low AChRAb. CONCLUSIONS: Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in pts with MG indicated to the treatment by PE suggest some systemic activation of immune response which is more pronounced in pts with high circulating AChRAb. PE led to the decrease of serum AChRAb and soluble adhesion molecules due to their effective filtration, but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with synthetic membrane.

Adult↗
PubMed1998

[Soluble TNF and IL-2 receptors in patients with breast carcinoma].

BACKGROUND: Cytokines were shown both to enhance tumour growth and formation of metastases and to inhibit proliferation of tumour cells. TNF alpha may mediate apoptosis and necrosis of cancer cells, the exact role of IL-2 remains to be elucidated. Plasma levels of TNF alpha and TNF and IL-2 soluble receptors (sTNF-R, sIL-2R) should thus be in some relation to the biological characteristics of the breast cancer. METHODS AND RESULTS: Plasma levels of TNF alpha, sTNF-R I and II and sIL-2R were measured in 31 women with different stages of breast cancer both before the institution of the therapy and after 3 months of the treatment. Plasma levels of both types of sTNF-Rs were higher in patients with breast cancer than in controls (sTNF-R I-2166.6 +/- 568.9 VS. 1121.3 +/- 260.6 pg/ml, p < 0.001, sTNF-R II-3792.8 +/- 958.9 vs. 1996.2 +/- 404.3 pg/ml, p < 0.001) with no significant difference between clinical stages. Plasma levels of both sTNF-R (0.871, p < 0.001) and sIL-2R tightly correlated one with each other. Plasma levels of TNF alpha decreased after treatment (from 3.92 +/- 1.86 to 3.40 +/- 1.15 pg/ml, p < 0.001), but plasma levels of sTNF-Rs and sIL-2R were not influenced by the treatment. CONCLUSIONS: Plasma levels of soluble TNF receptors may thus serve as a non-specific marker of the untreated breast cancer. Their relation to other biologic characteristics of this tumour is not clear. It remains also to be clarified if the long-term treatment leads to the normalization of sTNF-Rs plasma levels.

Adult↗
PubMed1998

[Interleukin-6, tumor necrosis factor alpha and their soluble receptors in Bence-Jones nephropathy. Possible role in pathogenesis andthe importance in the determination of prognosis in renal insufficiency].

BACKGROUND: Bence-Jones nephropathy, the most serious form of which is renal failure, is one of the frequent complications in multiple myeloma (MM). Precise pathogenetic mechanism of renal injury remains unclear. Experimental study points to the possible role of some cytokines in the development of this type of nephropathy. We have investigated the levels of interleukin-6 (IL-6), tumour nekrosis factor alpha (TNF-alpha) and their soluble receptors in patients with plasmocytoma. METHODS AND RESULTS: The group comprised 49 patients with plasmocytoma, mostly with MM. Significantly higher levels of IL-6 were found in patients with irreversible renal insufficiency and/or failure (group A-median 13.3 pg/ml, range 3.6-33.3) comparing patients with reversible impairment (group B-median 3.1-range 1.8-38.4) (p < 0.01) and those with normal renal functions (group C-median 2.3-range 0.97-7.41) (p < 0.01). Significant difference was also found between the groups B and C (p < 0.05). Analysis of variance with the use of various factors showed that the correlation between IL-6 and prognosis of renal disease was stronger (p < 0.001) than the correlation between cytokine levels and the clinical phase of MM (p < 0.05). The difference of IL-6 levels between various clinical stages of MM was not significant. The levels of sIL-6R were significantly increased in patients with both reversible and irreversible renal insufficiency comparing the group with unaffected renal functions (p < 0.05 and p < 0.01 respectively). TNF-alpha levels did not differ between all 3 groups of patients, however, significantly increased values of sTNF-R II were observed in group A vs B and group B vs C (p < 0.05). CONCLUSIONS: We conclude, that some cytokines, especially IL-6/sIL-6R, could play an important role in development of renal insufficiency in MM or other monoclonal gammapathies. We suggest that IL-6 levels could be predictive factor for renal insufficiency recovery.

Bence Jones Protein↗
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

[Vesicular and pronuclear glycoproteins in the pathogenesis of cholesterol lithiasis].

BACKGROUND: Several biliary proteins have been known to accelerate fusion of cholesterol rich phospholipid vesicles. Some of them are present in vesicular membrane, localisation of other proteins is unknown. Biliary glycoprotein has not been studied in consequence with pathogenesis of cholesterol lithiasis. METHODS AND RESULTS: Low molecular extravesicular proteins were separated from vesicles by gel filtration on a 1200mm column of Sephacryl S-300 HR. Immunoglobulins IgM, IgA, haptoglobin, biliary glycoprotein I (BGP I) and nonspecific crossreactive antigen were eluted along with vesicles. Albumin and alpha 1-acid glycoprotein were eluted later and must be extravesicular. CONCLUSIONS: Fact that BGP I (85 kDa membrane glycoprotein) eluted along with vesicles and not in albumin fraction suggests that it might be bound in vesicular membrane. As a known adhesion molecule it could thus play an important role in pathogenesis of cholesterol cholelithiasis.

Bile↗
PubMed1998

Neurotoxicity of tetraphenylporphinesulfonate (TPPS4) and a hematoporphyrin derivative (Photosan) in organotypic cultures of chick embryonic dorsal root ganglia.

The neurotoxic effect of tetraphenylporphinesulfonate (TPPS4) and a hematoporphyrin derivative (HPD, Photosan) has been studied in organotypic cultures of chick dorsal root ganglia maintained in a semi-solid culture medium. The changes in two characteristics of neurite outgrowth, the mean radial length of neurites growing out from the ganglia and the area of neurite outgrowths, are used as parameters to evaluate the toxic effect. The porphyrins are tested over the concentration range 10-160 micrograms ml-1. TPPS4 is slightly more toxic than the HPD Photosan. The median inhibitory concentration (IC50) for TPPS4 is 45-50 micrograms ml-1 and for the HPD Photosan 50-60 micrograms ml-1, respectively. Nevertheless, the toxicity of the two drugs is relatively low compared to that of commonly used anticancer drugs, such as cisplatin or taxol.

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↗
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↗
PubMed1997

Photodynamic effects of meso-tetra (4-sulfonatophenyl)porphine on human leukemia cells HEL and HL60, human lymphocytes and bone marrow progenitor cells.

Meso-tetra(4-sulfonatophenyl)porphine (TPPS4), in combination with a light dose of 14 J cm-2, has a profound negative effect on the proliferation and viability of leukemia cells HL60 (human promyelocytic leukemia) and HEL (human erythroleukemia), the viability of normal lymphocytes and the colony-forming activity of human bone marrow progenitor cells. However, normal leukocytes (monocytes, granulocytes) are, to a large extent, resistant to photodynamic treatment (PDT). Whilst DNA fragmentation suggesting apoptosis is induced in HL60 cells, accumulation in the interphase of the cell cycle (G0/G1, G2/M) is mainly operative in the TPPS4-mediated PDT of HEL cells. The "dark" effect of TPPS4 on the cell viability is below 15% up to a concentration of 40 microM.

Bone Marrow Cells↗
PubMed1997

Cytokine profile in autosomal dominant polycystic kidney disease.

To elucidate the pathogenetic mechanism of renal parenchymal injury in autosomal dominant polycystic kidney disease (ADPKD) patients, typically characterized by renal cystic changes paralleled by interstitial inflammation and gradual fibrotic changes, the role of selected inflammatory mediators was evaluated in a group of ADPKD patients with normal glomerular filtration rate. The plasma concentrations of IL-6, IL-8, ICAM-1 and VCAM-1 (which may reflect systemic response to inflammation/infection) were increased in the ADPKD patient group. Coupled with decreased urinary excretion of the IL-1 receptor antagonist (which exerts an anti-inflammatory role), these results suggest that even in overt infection free status, the proinflammatory system is more activated and anti-inflammatory defence system weakened in ADPKD subjects. Our data support the current view that cytokines are candidate contributors to pathogenesis of ADPKD.

Adult↗
PubMed1997

Incomplete distal renal tubular acidosis coinherited with a mutation in the band 3 (AE1) gene.

BACKGROUND: Band 3 (anion exchanger 1, AE1) is one of the most abundant proteins of the erythrocyte membrane. We have previously characterized twenty AE1 gene defects underlying spherocytic haemolytic anaemia with band 3 deficiency. Since AE1 is also expressed in the intercalated cells of renal cortical collecting ducts where it is thought to participate in urine acidification, we asked whether the spherocytogenic AE1 mutations also affect the regulation of urine acidity. METHODS: We examined 10 patients from seven unrelated families with hereditary spherocytosis with band 3 deficiency using the short urine acidification test with CaCl2 administration at a dose of 0.2 g/kg b.w. To asses the ability of the nephron to secrete protons, 400 ml of NaHCO3 were infused over a period of 2 h. RESULTS: While we detected no significant abnormalities in eight patients, we have diagnosed incomplete distal renal tubular acidosis (dRTA) in two patients from one family whose urinary pH 5 h after CaCl2 administration were 6.56 and 6.89. Administration of bicarbonate in these two patients resulted in high urinary HCO3- concentration. The patients carry the previously characterized mutation band 3PRIBRAM that encodes a C-terminally truncated band 3 containing only the cytoplasmic domain and the first three putative transmembrane segments. CONCLUSIONS: This finding shows an association of a band 3 defect with abnormal urinary acidification perhaps secondary to Cl-/HCO3- exchange in the basolateral membrane of alpha-intercalated cells of cortical collecting ducts.

Acidosis↗