Suppression of Mesangial-Cell Proliferation by Trapidil in Glomerulonephritis Induced by Anti-Thymocyte Serum in Rats

1995 ◽  
Vol 23 (6) ◽  
pp. 458-466 ◽  
Author(s):  
M S Razzaque ◽  
M Cheng ◽  
T Taguchi
Keyword(s):  
Cell Proliferation ◽  
Body Weight ◽  
Single Dose ◽  
Growth Factor ◽  
Mesangial Cell ◽  
Platelet Derived Growth Factor ◽  
Group Iii ◽  
Group I ◽  
Mesangial Cell Proliferation ◽  
Group Ii

Trapadil (Mochida Pharmaceuticals, Japan), an antiplatelet drug, suppresses the growth of several cell types and is thought to antagonize platelet-derived growth factor. The effects of trapidil on mesangial-cell proliferation in glomerulonephritis induced by anti-thymocyte serum in Wistar rats were investigated. Control rats were treated with phosphate-buffered saline (group I); group II rats were injected with a single dose of anti-thymocyte serum (8 ml/kg body weight), and group III rats were treated with both a single dose of anti-thymocyte serum (8 ml/kg body weight) and with trapidil (5 mg/kg body weight/day). Three rats in each group were killed on day 3, and the other three on day 10. Control rats showed no significant histological changes on day 3 or day 10. In group II, on day 3, there was a marked decrease in glomerular cell numbers, with mesangiolysis. Histologically severe mesangial-cell proliferation with expansion of mesangial areas was noted on day 10. None of the rats in group III showed mesangial alterations, histologically, indicating that mesangial-cell proliferation was suppressed by trapidil. This suppression may result from antagonism of the binding of platelet derived growth factor to the specific surface receptors in the mesangial cells. Trapidil may have clinical value in the treatment of mesangial-cell proliferative glomerular diseases.

ANABOLIC STEROID AND INTRAPULMONARY HEPARIN IN THE PREVENTION OF POSTOPERATIVE DEEP VEIN THROMBOSIS

1987 ◽  
Author(s):  
K Zawilska ◽  
A Tokarz ◽  
P Psuja ◽  
P Szymczak ◽  
S Kawczyński ◽  
...  
Keyword(s):  
Body Weight ◽  
Deep Vein Thrombosis ◽  
Single Dose ◽  
Anabolic Steroid ◽  
Group Iii ◽  
Vein Thrombosis ◽  
Group I ◽  
Group Ii ◽  
Long Acting ◽  
Deep Vein

150 patients over 40 years old undergoing major abdominal surgery were divided into 3 groups:1/ group I - receiving a single injection of long acting anabolic steroid /nandrolone phenylpropio-nate, 50 mg intramusculary/ a day prior to surgery 2/ gropup II - receiving the same dose of anabolic steroid plus a single dose of heparin /800 U/kg of body weight/ intrapulmonary a day prior to surgery 3/ group III - receiving only a single dose of heparin /800 U/kg of body weight/ intrapulmonary a day prior to surgery.The deep vein thrombosis /DVT/ was detected using the 125 I-fibrinogen test. The occurence of DVT was:in group I - 14%in group II - 4%in group III - 8%There were no detectable haemorrhagic complications in patients of group I and III, in 6% of patients of group II a sgliht increase of intraoperative bleeding and/or wound hematoma appeared.We conclude that prophylaxis of DVT in the postoperative period with the single dose of anabolic steroid and intrapulmonary heparin is an effective, safe and easy to handle procedure.

Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival

2001 ◽  
Vol 101 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Chiyoko N. INOUE ◽  
Isao NAGANO ◽  
Ryo ICHINOHASAMA ◽  
Natsumi ASATO ◽  
Yoshiaki KONDO ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Growth Factor ◽  
Lysophosphatidic Acid ◽  
Culture Medium ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Platelet Derived Growth Factor ◽  
P53 Expression ◽  
Mesangial Cell Proliferation

Although mesangial cell death has been shown to be correlated with mesangial cell mitosis in vivo, little is known about how these two apparently opposite events are regulated. We show that the addition of platelet-derived growth factor (PDGF; 10–50 ng/ml) to primary cultured rat mesangial cells for 24 h caused continuous proliferation along with simultaneous cell death. This process was accompanied by the fragmentation of DNA into nucleosomal oligomers, the development of apoptotic morphological changes in the nucleus, and increased expression of p53. Accumulation of lactate dehydrogenase (LDH) was also observed in the culture medium, suggesting that both apoptosis and necrosis are involved in the cell death mechanisms observed. We also observed that addition of 30 µM lysophosphatidic acid (LPA) to the culture medium greatly suppressed PDGF-induced cell death, leading to synergistically enhanced mesangial cell proliferation. DNA fragmentation, p53 expression and LDH release were all suppressed by LPA. We suggest that PDGF is a bifunctional molecule in mesangial cells that evokes both cell proliferation and cell death simultaneously, whereas LPA is a survival factor. We speculate that PDGF and LPA may play important roles in the progression or exacerbation of proliferative glomerulonephritis.

Repeated Intraportal Injections of Subtherapeutic Islet Cell Isografts Restore Normoglycemia in Streptozotocin-Diabetic Rats

1997 ◽  
Vol 6 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Eugenio Morsiani ◽  
Jacek Rozga ◽  
Giovanni Dellagiacoma ◽  
Achilles A. Demetriou
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Diabetic Rats ◽  
Metabolic Effects ◽  
Intravenous Glucose ◽  
Group Iii ◽  
Group I ◽  
Streptozotocin Diabetic Rats ◽  
Group Ii ◽  
Normal Controls

Poor engraftment and consequent loss of β-cell mass could be one of the factors that are responsible for function loss after intraportal islet transplantation (Tx). Streptozotocin-diabetic rats were transplanted with syngeneic islets, which were injected into the portal vein via an indwelling catheter connected to a subcutaneous port. In Group I (n = 6), 1,000 islets were injected in a single dose into the liver. In Group II (n = 6), five doses of 200 islets were repeatedly injected over a period of 14 days, for a total of 1,000 islets. In Group III (n = 4), five decreasing doses of islets were injected over a period of 14 days, for a total of 750 islets. Nonfasting blood glucose (n-FBG) and body weight (b.wt.) were determined twice a week and an intravenous glucose tolerance test (IVGTT) was performed at 30 and 90 days. In Group I, n-FBG decreased in 2 wk from the time of first islet injection, averaging 110 ± 21.9 mg/dL at 1 mo (p < 0.05 vs. normal controls); this value was maintained throughout the 3-mo duration of the study. In Group II, n-FBG was normalized in 2 wk averaging 90.2 ± 25 mg/dL on day 12 (p = NS vs. normal controls) and 75.8 ± 14.6 mg/dL at 1 month (p = NS vs. normal controls); this value was maintained throughout the 3-mo duration of the study. In Group III, n-FBG decreased to normal values in 2 wk, averaging 77 ± 15.7 mg/dL at 1 mo (p = NS vs. normal controls), but normoglycemia was maintained for 40 days and then followed by a progressive increase. Only in Group II, KG (percent/min decline in glucose level) was not significantly different from that of normal controls (1.702 ± 0.531 at 1 mo and 1.676 ± 0.891 at 3 mo), while it was significantly lower than normal controls in both Group I and III animals. Body weight increase after Tx correlated with the number of transplanted islets and at 90 days, Group III rats showed less increase than Groups I and II (p < 0.05), while no significant differences in b.wt. were recorded between Group I and II. The findings indicate that intraportal islet Tx, injected repeatedly and in small doses, produced better metabolic effects than injection of the same total number of islets in a single dose. Copyright © 1997 Elsevier Science Inc.

scholarly journals Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor.

1992 ◽  
Vol 175 (5) ◽  
pp. 1413-1416 ◽  
Author(s):  
R J Johnson ◽  
E W Raines ◽  
J Floege ◽  
A Yoshimura ◽  
P Pritzl ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Wound Repair ◽  
Mesangial Cell ◽  
Platelet Derived Growth Factor ◽  
Inflammatory Conditions ◽  
Mesangial Cell Proliferation ◽  
Matrix Expansion

Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells in culture, is expressed in vivo in a variety of inflammatory conditions associated with cell proliferation, including atherosclerosis, wound repair, pulmonary fibrosis, and glomerulonephritis. However, it is not known if PDGF mediates the fibroproliferative responses that characterize these inflammatory disorders. We administered neutralizing anti-PDGF IgG or control IgG to rats with mesangial proliferative nephritis. Inhibition of PDGF resulted in a significant reduction in mesangial cell proliferation, and largely prevented the increased deposition of extracellular matrix associated with the disease. This suggests that PDGF may have a central role in proliferative glomerular disease.

Interactions of Hydrogen Peroxide with Interleukin-6 and Platelet-Derived Growth Factor in Determining Mesangial Cell Growth: Effect of Repeated Oxidant Stress

1993 ◽  
Vol 85 (6) ◽  
pp. 747-751 ◽  
Author(s):  
R. J. D'Souza ◽  
H. M. Phillips ◽  
P. W. Jones ◽  
R. C. Strange ◽  
G. M. Aber
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Interleukin 6 ◽  
Mesangial Cell ◽  
Thymidine Incorporation ◽  
Mesangial Cells ◽  
Platelet Derived Growth Factor ◽  
Growth Effect ◽  
Cell Counts ◽  
Mesangial Cell Proliferation

1. This study examined the influence of H2O2, interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H2O2 (10−8-10−4 mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [3H]thymidine incorporation and cell counts. 2. Although one pulse of H2O2 had no significant effect on mesangial cell proliferation, three daily pulses of 10−6 mol/l H2O2 resulted in a significant increase in [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) (P <0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [3H]thymidine incorporation increasing by 19 (36.7, −6.7)% (P <0.05) and 53.5 (107, 21.9)% (P <0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10−6 mol/l H2O2 [49.9 (77.7, 12.3)%] (P <0.01), whereas the addition of 10−6 mol/l H2O2 to platelet-derived growth factor resulted in a summated increase in [3H]thymidine incorporation of 82.7 (113, 57.4)% (P <0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 103)% (P <0.05). 3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.

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