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F Thaiss

Publications and source records attributed to F Thaiss.

At least 37 records · Page 2Linked to original sources
PubMed1996

Angiotensin-converting enzyme inhibition in experimental in-situ immune complex glomerulonephritis: influence on renal function, proteinuria, and morphology.

BACKGROUND: Converting enzyme inhibition (CEI) ameliorates progressive loss of function in non-immune-mediated renal diseases and experimental hypertension. Little, however, is known on the potential role of CEI in established experimental chronic glomerular immune injury. We therefore studied the effect of the CEI ramipril on renal function and morphology in a model of immune mediated glomerular injury. METHODS: The immune complex glomerulonephritis was induced in uninephrectomized rats by intrarenal perfusion with the cationized antigen followed by an intravenous application of the antibody. This disease is characterized by the development of progressive albuminuria and a nephrotic syndrome (albuminuria: immune complex glomerulonephritis 342 +/- 58, control 76 +/- 18 mg/24h; P < 0.001). The CEI by ramipril, dissolved in the drinking water, was given 28 weeks after induction of the disease and treatment was continued for 12 weeks. RESULTS: In these experiments ramipril significantly reduced albumin excretion (immune complex glomerulonephritis + CEI 109 +/- 16 mg/24h; P < 0.01) when compared with untreated nephritic rats. Ramipril, however, did not significantly change inulin clearances (immune complex glomerulonephritis 224 +/- 67, immune complex glomerulonephritis + CEI 278 +/- 48 microliters/min/100 g bw). Glomerular structural damage expressed as glomerular damage index was significantly greater in rats with immune complex glomerulonephritis when compared with controls (immune complex glomerulonephritis 0.91 +/- 0.13; control 0.60 +/- 0.08; P < 0.05), but was uneffected by the treatment with the CEI (immune complex) glomerulonephritis + CEI 1.02 +/- 0.26; control + CEI 0.63 +/- 0.11). CONCLUSIONS: These data demonstrate that ramipril reduced albuminuria in a model of immune complex glomerulonephritis; however, it failed to alter GFR and glomerular damage index. The study suggests that ramipril ameliorates proteinuria independently of obvious glomerular histological changes. The reduction of proteinuria is, however, associated with a significant decrease in filtration fraction and therefore is at least partially haemodynamically mediated.

Albuminuria↗
PubMed1996

[The kidney in diabetes mellitus--new aspects on pathogenesis, diagnosis and therapy].

The knowledge about the pathogenesis of the diabetic nephropathy has significantly increased during the last years. The diabetic nephropathy is one of the best treatable renal disease due to the treatment strategies derived from this knowledge and the new emerging therapeutic perspectives. However, it is a prerequisite that the treatment is started early in the course of the disease. The onset of microalbuminuria is currently the known indication for the development of a nephropathy in a patient with diabetes. Additional to the intensified insulin treatment, the application of an ACE-inhibitor should be taken into account when microalbuminuria occurs.

Albuminuria↗
PubMed1995

Cyclosporine stimulates expression of transforming growth factor-beta in renal cells. Possible mechanism of cyclosporines antiproliferative effects.

CsA induces a reversible inhibition of proliferation in cultured murine proximal tubular cells (MCT cells) and syngeneic tubulointerstitial fibroblasts (TFB). To test whether this effect may be caused by endogenous synthesis and release of transforming growth factor-beta 1 (TGF-beta 1), a well-known inhibitor of mitosis, MCT cells and TFB grown in serum-free media were treated with different concentrations of CsA. CsA, in a dose-dependent manner in a range of 500-2000 ng/ml, stimulated expression of TGF-beta 1 protein and steady-state mRNA levels in both cell lines (MCT cells: controls, 9.3 +/- 1.0; 1500 ng/ml CsA, 19.1 +/- 6.1 pg TGF-beta 1/10(3) cells [P < 0.05 vs. controls]; TFB: controls, 5.4 +/- 0.9; 1500 ng/ml CsA, 7.7 +/- 0.3 pg TGF-beta 1/10(3) cells; n = 6). Short-term daily intraperitoneal injections of CsA (40 mg/kg body weight/day) into SJL mice for 1 and 4 weeks also induced an increase in whole kidney levels of TGF-beta 1 mRNA. Incubation of MCT cells and TFB with CsA in the presence of 30 micrograms/ml of a neutralizing anti-TGF-beta 1-3 mAb partly reversed the cell cycle arrest induced by CsA. These data suggest that CsA-mediated intrarenal synthesis and release of TGF-beta 1 may play a role in the CsA-induced growth arrest and might therefore be relevant in the development of chronic CsA nephrotoxicity, which is characterized by striped fibrosis and tubular atrophy.

Animals↗
PubMed1995

[Treatment of thrombotic thrombocytopenic purpura (Moschcowitz's disease) with vincristine].

A 64-year old female had been diagnosed as having thrombotic thrombocytopenic purpura (TTP; Moschcowitz syndrome) in 1984. The initial episode and one recurrence 5 years later were successfully treated with fresh plasma transfusions without plasmapheresis. Two days before the present admission, she noticed pain in the knee and haematomas in both legs. Marked thrombocytopenia (9000/microliters), haemolytic anaemia (lactate dehydrogenase 1800 U/l, haemoglobin 7.8 g/dl, haptoglobin 5 mg/dl) and skin haemorrhages suggested a second recurrence of TTP. The blood film showed a massive increase in fragmented cells (more than 30 per field), microspherocytes and normoblasts. Thrombocyte values initially rose on daily treatment with plasmapheresis using membrane separation and fresh plasma exchange. However, after two attempts at stopping therapy, plasmapheresis and fresh plasma replacement failed to normalise thrombocyte values. The patient had a total of 44 plasmaphereses. Intravenous administration of three doses of 1.5 mg vincristine at intervals of 7 and 5 days combined with further plasmapheresis treatment soon led to normalisation of the thrombocyte count (320,000/microliters), a fall in lactate dehydrogenase (120 U/l) and a disappearance of fragment cells in the blood smear. The patient is still in complete remission 6 months after stopping treatment. Treatment with vincristine should be considered for TTP refractory to treatment.

Bone Marrow Examination↗
PubMed1995

Characterization of the mononuclear cell infiltrate in the glomerulus of rats with glomerulonephritis.

Bone marrow-derived inflammatory cells contribute to glomerular damage in experimental glomerulonephritis. The time sequential appearance and the pattern of inflammatory cells in the diseased glomerulus is, however, unclear. We therefore characterized the inflammatory cell infiltrate in a model of unilateral in situ immune complex glomerulonephritis. The cellular infiltrate was specific for the diseased kidney and independent of changes in peripheral blood or spleen. We found an influx of leukocyte common antigen (LCa)-positive and ED1-positive (monocytes/macrophages) cells in isolated glomeruli as early as 24 h after induction of the disease. Lymphocytes of the CD4-, CD8- and CD20-positive phenotypes were present in diseased glomeruli at Day 10. Complement depletion prevented the influx of monocytes/macrophages at 24 h in the glomerulus, which indicates that complement activation is important for the glomerular cell infiltrate at this early time point. The results demonstrate that the inflammatory cell infiltrate is regulated in situ at the glomerular level and not accompanied by similar changes in peripheral blood and spleen cells.

Animals↗
PubMed1994

The effect of prostaglandin E2 on mRNA expression and secretion of collagens I, III, and IV and fibronectin in cultured rat mesangial cells.

The possible role of prostaglandin E2 (PGE2) on the formation of collagens and fibronectin in cultured rat mesangial cells (MC) was studied. The effect of exogenous PGE2 was analyzed by the measurement of steady-state mRNA levels of the extracellular matrix components and by the secretion of these matrix components into cell culture supernatants. PGE2, in a dose-dependent manner, reduced mRNA levels of alpha 1(I) and alpha 1(III) procollagens but had little effect on alpha 1(IV) procollagen and fibronectin mRNA. In addition to its role on mRNA levels, PGE2 reduced the secretion of all studied collagen types into the cell culture supernatants. To evaluate a possible role of intracellular cAMP in the mediation of the PGE2 effects, MC were incubated with the cAMP analogue 8-bromo-cAMP (8brcAMP). In contrast to PGE2, 8brcAMP (1 mM) had no effect on mRNA expression of procollagen Types I and III over the studied time period (1 to 48 h). Furthermore, 8brcAMP stimulated collagen secretion into the cell supernatant after 48 h of incubation. These data demonstrate that PGE2 reduces mRNA levels of procollagen Types I and III in cultured MC, although the biosynthesis of all studied extracellular matrix components is inhibited. These alterations seem to be independent of intracellular cAMP, because the cAMP analogue 8brcAMP does not mimic the PGE2 effects on steady-state mRNA expression and collagen secretion of the studied extracellular matrix components.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Platelet-activating factor receptor antagonist improves renal function and glomerular lesions in renal ablation.

In the renal ablation model hemodynamic changes, glomerular hypertrophy, and the release of inflammatory mediators contribute to structural damage and functional changes. Platelet-activating factor (PAF) has both hemodynamic and immune-mediating properties. We therefore examined the role for a PAF receptor antagonist (WEB 2170) on glomerular hemodynamic function, albuminuria, and structural alterations in a rat model of renal ablation (Nx). WEB 2170 treatment was started 10 weeks after renal ablation, and the variables were assessed at 36 weeks after surgery. WEB 2170 significantly improved inulin and PAH clearances at 36 weeks (inulin clearance: Nx, 182 +/- 28 microliters/min/100 gm body weight; Nx plus WEB, 284 +/- 19 microliters/min/100 gm body weight; p < 0.05; PAH clearance: Nx, 718 +/- 85 microliters/min/100 gm body weight; Nx plus WEB, 1215 +/- 103 microliters/min/100 gm body weight; p < 0.05). Glomerular prostaglandin E2 (PGE2) formation was significantly increased in nephrectomized rats treated with WEB 2170 when compared with nephrectomized animals not treated (PGE2: Nx, 103 +/- 16 pg/min/mg protein; Nx plus WEB, 182 +/- 19 pg/min/mg protein; p < 0.01). The PAF receptor antagonist did not change albuminuria (Nx, 205 +/- 56 mg/24 hr; Nx plus WEB, 178 +/- 48 mg/24 hr). Glomeruli of rats treated with WEB 2170 had significantly fewer sclerotic lesions at 36 weeks when compared with untreated animals (Nx, 36.5 +/- 4.4%; Nx plus WEB, 19.3 +/- 3.7%; p < 0.05). The results demonstrate that a PAF receptor antagonist significantly improves whole kidney clearances and glomerular morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1994

Microangiopathic hemolytic anemia and renal impairment following autologous bone marrow transplantation: a case of hemolytic uremic syndrome?

Thrombotic microangiopathy, which encompasses both thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), is a severe and life-threatening complication following bone marrow transplantation (BMT). It has been reported after allogeneic BMT but may also occur after autologous BMT. Here we describe a case of microangiopathic hemolytic anemia and progressive renal failure subsequent to autologous BMT.

Anemia, Hemolytic↗
PubMed1993

TNF alpha induces expression of the chemoattractant cytokine RANTES in cultured mouse mesangial cells.

We investigated the effect of several immune-relevant cytokines on expression of the chemoattractant intercrine/chemokine RANTES in a mouse mesangial cell line (MMC). Fifty ng/ml recombinant tumor necrosis factor alpha (TNF alpha) induced a marked increase in RANTES transcripts after two hours. RANTES mRNA remained elevated for 24 to 48 hours after stimulation, and could be abolished by co-incubation with 30 micrograms/ml of a neutralizing rabbit anti-TNF alpha antibody. Protein expression of RANTES, as assessed by indirect immunofluorescence and Western blotting, increased in MMCs 24 hours after TNF alpha stimulation. Interleukin-1 beta, tumor necrosis factor beta (TNF beta), and lipopolysaccharide (LPS) also increased expression of RANTES mRNA. In addition, RANTES mRNA expression was stimulated in glomeruli harvested from rats following renal in vivo perfusion with TNF alpha. Our results indicate that mesangial cells produce the small cytokine RANTES. This factor, in concert with other chemoattractants, may play a role in the glomerular recruitment of inflammatory cells like macrophages/monocytes.

Animals↗
PubMed1993

Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis.

The infiltration of monocytes-macrophages in the glomerulus is one of the hallmarks of glomerulonephritis and may play an important pathogenetic role. Monocyte chemoattractant protein-1 (MCP-1) and colony stimulating factor-1 (CSF-1) are monocyte-specific cytokines with chemoattractant and activating activities for monocytes. MCP-1 and CSF-1 can be generated by several cell types, including glomerular mesangial cells, and can be stimulated by cytokines and immune complexes. To study the expression of CSF-1 and MCP-1 in a model of proliferative glomerulonephritis we used Northern blot analysis and immuno-histochemistry. The glomerular lesion was induced in rats by the i.v. injection of a heterologous anti-thymocyte antiserum (ATS), directed against an antigen which is localized on glomerular mesangial cells. Northern blot analysis revealed comparable amounts of CSF-1 in glomeruli isolated from control untreated rats, and from rats after 30 minutes to three weeks of injection of ATS antibody. In control glomeruli no mRNA levels for MCP-1 were detectable, but increased markedly 30 minutes after the induction of the nephritis, were then reduced at 24 hours and increased again at 5 and 21 days after induction of the disease. The increase in mRNA levels for MCP-1 30 minutes or 24 hours after ATS injection was markedly attenuated if rats were complement depleted by cobra venom injection. These time points following antibody injection were associated with mesangial immune complex formation (30 min), mesangiolysis (24 hr) and proliferative glomerulonephritis (5 and 21 days). By immunohistology the presence of MCP-1 was demonstrated in glomeruli with a predominant mesangial distribution. The mesangial immunofluorescence for MCP-1 followed a pattern similar to that of the mRNA for MCP-1 after induction of the disease process, that is, it increased after 30 minutes, decreased after 24 hours and was increased again at three weeks. Within 30 minutes of the antibody injection an increased infiltration of monocytes-macrophages was observed in the glomeruli, which was maintained up to three weeks of induction of the glomerulonephritis. When the rats were decomplemented with cobra venom factor prior to the i.v. injection of ATS, the expression of MCP-1 in glomeruli remained low and the influx of monocytes/macrophages did not appear. We conclude that MCP-1 is increased early on in glomeruli of rats with immune-mediated mesangial proliferative glomerulonephritis. This increase is mediated by complement activation secondary to the in situ immune complex formation at the glomerular mesangium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

TGF-beta stimulates rat mesangial cell proliferation in culture: role of PDGF beta-receptor expression.

Transforming growth factor (TGF)-beta is known to increase mesangial cell (MC) matrix; however, its possible role on MC proliferation is controversial. We therefore studied the influence of TGF-beta on MC proliferation in culture and evaluated its effect on the platelet-derived growth factor (PDGF) B-chain as well as the expression of the PDGF beta-receptor. TGF-beta (1 ng/ml) increases MC DNA synthesis by approximately threefold after 48 h of incubation. TGF-beta-induced MC proliferation was also confirmed by cell counts. A neutralizing anti-TGF-beta antibody completely blocked this growth promoting activity. The levels of PDGF beta-receptor steady-state mRNA were increased by TGF-beta at 48 h. This was associated with an increase in receptor density per cell as measured by receptor kinetic studies. PDGF B-chain mRNA was also increased by TGF-beta at 48 h. A neutralizing anti-PDGF B-antibody causes no reduction of TGF-beta-induced DNA synthesis; however, suramin completely inhibited the mitogenic effect of TGF-beta. We conclude that TGF-beta stimulates MC growth in long-term culture, a process in which upregulation of the PDGF beta-receptor and enhanced synthesis of PDGF B-chain might be involved.

Animals↗
PubMed1993

[Therapy of diabetic nephropathy].

New pathophysiological insights in the last few years on the development of diabetic nephropathy have led to a change in therapeutic measures. The emphasis is put on preventive considerations for the insulin-dependent diabetic patient. Strict control of glycemia and the early use of an angiotensin-conversion inhibitor are of importance. Therapy of the manifest diabetic nephropathy is based on strict metabolic control combined with reduced protein intake. Furthermore, an often co-existing hypertension needs to be treated. Normotensive blood pressure should be obtained. ACE-inhibitors and Ca-antagonists have been proven to be very effective, although there seem to exist differences in the type of Ca-antagonists regarding effectiveness on albuminuria. The combination of ACE-inhibitors and Ca-antagonists seems to have an additional beneficial impact on albuminuria. A significant decrease in the loss of glomerular function and a decrease in albuminuria can be obtained by consistent consideration of these therapeutic strategies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury.

To evaluate whether monocytes/macrophages derived from glomeruli could be a source of increased eicosanoid and free oxygen radical formation in glomerular disease, monocytes/macrophage (M/M) were isolated from nephritic glomeruli and their in vitro generation of eicosanoids and superoxides were measured. Glomerular immune injury was induced by i.v. injection of a rabbit-anti-rat thymocyte antiserum (ATS). Kidneys were removed two, five, and 24 hours, and three and eight days after ATS. Adhesive glomerular macrophages were obtained by isolation of glomeruli, enzymatic digestion and incubation of the single cell suspensions in culture dishes. O2-production was evaluated by superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome C; PGE2 and TxB2 release was assessed by direct RIA. Glomerular macrophage infiltration was maximal 24 hours after intravenous antibody (35.9 +/- 5.1 M/M per glomerulus). In vitro production of superoxide was significantly enhanced (P less than 0.001) five hours after ATS administration (51.6 +/- 4.4 nmol O2/10(6) MM/hr), when compared with M/M from controls (30.4 +/- 2.0 nmol O2/10(6) MM/hr). TxB2 formation of glomerular M/M was increased (P less than 0.001) two hours and five hours after ATS administration (1056 +/- 75 and 1182 +/- 112 pg TxB2/10(6) MM/hr) compared with controls (390 +/- 34 pg TxB2/10(6) MM/hr). PGE2 synthesis, however, was decreased (P less than 0.01) at five hours after ATS (629 +/- 43 pg PGE2/10(6) MM/hr) compared with controls (950 +/- 125 pg PGE2/10(6) MM/hr). Furthermore, there was release of leukotriene B4 (LTB4) in monocytes of nephritic glomeruli five hours after ATS administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Thromboxane mediates glomerular haemodynamics in a model of chronic glomerular disease.

In order to evaluate a possible haemodynamic role of cyclooxygenase products in chronic renal disease, a model of chronic glomerular injury was induced in nephritic rats by unilateral nephrectomy and high dietary protein intake. Eight weeks after induction of an in situ immune complex glomerulonephritis (CGN), rats subjected to high protein (HP) intake (42% protein) and uninephrectomy revealed a significantly lower glomerular filtration rate (GFR; 485 +/- 53 microliters min-1 100 g-1 body weight (BW)) compared with uninephrectomized rats with ICGN which were on low protein (LP) diet (6% protein) (825 +/- 155 microliters min-1 100 g-1 BW) (P less than 0.01). The glomerular thromboxane B2 (TxB2) formation in uninephrectomized rats with ICGN on either LP or HP intake was not significantly different (HP: 473 +/- 61; LP: 493 +/- 63 pg mg-1 min-1), but was significantly higher when compared with non-nephritic controls on either diet. Glomerular prostaglandin E2 (PGE2) production in rats on HP diet was higher compared with rats with LP intake (HP: 617 +/- 67; LP: 351 +/- 76 pg mg-1 min-1) (P less than 0.01). The thromboxane receptor blocker daltroban significantly elevated suppressed GFR in ICGN rats on HP diet (ICGN+vehicle: 426 +/- 69; ICGN+daltro: 689 +/- 66 microliters min-1 100 g-1 BW) (P less than 0.01). Thromboxane receptor blockade had no effect on glomerular haemodynamics in ICGN animals receiving LP diet (ICGN+vehicle: 771 +/- 24; ICGN+daltro: 684 +/- 85 microliters min-1 100 g-1 BW).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Morphologic and functional consequences of immune-mediated mesangiolysis: development of chronic glomerular sclerosis.

The i.v. injection of a rabbit anti-rat thymocyte serum (ATS) induces mesangiolysis in rats, followed by a mesangioproliferative glomerulonephritis (4 to 7 days after antibody). This proliferative lesion disappears 4 to 6 wks after antibody. In order to induce an antibody-mediated sclerotic glomerular disease, uninephrectomized rats received ATS twice at 6-wk interval. At 6 months after the first antibody injection, albuminuria, arterial blood pressure, and inulin clearances were evaluated and renal morphologic studies were performed. At the time of evaluation, mean arterial blood pressure and inulin clearances were not different between animals that received the antibody and uninephrectomized controls. Rats that were injected with antibody, however, had significantly higher albuminuria compared with that of controls. Glomeruli of rats with ATS revealed expansion of the glomerular mesangial matrix and focal sclerosis. A semiquantitative morphologic analysis revealed an increased incidence of glomerular lesions and a higher glomerular damage index in kidneys of nephritic rats. These data demonstrate that the repetitive injection of ATS to unilaterally nephrectomized rats induces a model of chronic glomerular sclerosis.

Albuminuria↗