Effect of two Forms of Granulocyte-Colony-Stimulating Factor on Hepatic Regeneration after 70% Partial Hepatectomy in Rats

1997 ◽  
Vol 92 (3) ◽  
pp. 315-320 ◽  
Author(s):  
Stamatios E. Theocharis ◽  
Emmanuel B. Agapitos ◽  
Alexandra P. Margeli ◽  
Nicolaos D. Goutas ◽  
Christos N. Kittas ◽  
...  
Keyword(s):  
Body Weight ◽  
Partial Hepatectomy ◽  
Proliferating Cell Nuclear Antigen ◽  
Kinase Activity ◽  
Nuclear Antigen ◽  
Hepatic Regeneration ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Proliferating Cell ◽  
Stimulating Factor

1. The purpose of this study was to determine whether the commercially available forms of granulocyte-colony-stimulating factor exert the same beneficial effect on hepatic regeneration after 70% partial hepatectomy in rats. Adult male Wistar rats received either the two commercially available forms of granulocyte-colony-stimulating factor (Filgrastim or Lenograstim), or saline, simultaneously with partial hepatectomy. Hepatic regeneration was documented by determining [3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity, mitotic index and proliferating cell nuclear antigen immunostaining, at various time points after partial hepatectomy. 2. DNA biosynthesis, liver thymidine kinase activity and mitotic index of hepatocytes were not only enhanced (P < 0.001) in rats that received 150 μg of Filgrastim or Lenograstim/kg of body weight, but occurred earlier than in saline-treated partially hepatectomized rats. The administration of both forms of granulocyte-colony-stimulating factor, at the dose of 15 μg/kg of body weight, did not affect liver proliferative capacity, compared with observations in simply partially hepatectomized rats. High mitotic and proliferating cell nuclear antigen indices appeared earlier than those estimated in simply partially hepatectomized rats, when 150 μg of Filgrastim or Lenograstim/kg of body weight were administered. 3. These findings suggest that both pharmacologically available forms of granulocyte-colony-stimulating factor at a dose of 150 μg/kg of body weight are able to augment liver regenerative capacity, to the same extent, in this animal model of controlled hepatie proliferation.

scholarly journals Effect of the aqueous extract of Sida cordifolia on liver regeneration after partial hepatectomy

2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 37-39 ◽  
Author(s):  
Renata Lemos Silva ◽  
Gustavo Barreto de Melo ◽  
Valdinaldo Aragão de Melo ◽  
Ângelo Roberto Antoniolli ◽  
Paulo Roberto Teixeira Michellone ◽  
...  
Keyword(s):  
Oral Administration ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Aqueous Extract ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Hepatic Regeneration ◽  
Control Group ◽  
Sida Cordifolia ◽  
Proliferating Cell

PURPOSE: The use of medicinal plants for the treatment of human diseases has increased worldwide. Many of them are used by oral administration and, after absorption, may affect many organs. Therefore, this study aimed at assessing the effects of the aqueous extract of Sida cordifolia leaves, popularly known in Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were divided into four groups: control, Sida100, Sida200 and Sida400 groups. All animals were submitted to oral administration of distilled water, 100, 200 and 400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately after this, they underwent 67% partial hepatectomy. Twenty four hours later, their livers were removed. Hepatic regeneration was assessed by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed higher liver regeneration indices than control group (p<0.001 and p<0.05, respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates liver regeneration after 67% partial hepatectomy in rats.

scholarly journals Association of proliferating cell nuclear antigen with cyclin-dependent kinases and cyclins in normal and transformed human T lymphocytes

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3413-3421 ◽  
Author(s):  
A Szepesi ◽  
EW Gelfand ◽  
JJ Lucas
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cell Line ◽  
Proliferating Cell Nuclear Antigen ◽  
Kinase Activity ◽  
Jurkat Cells ◽  
Nuclear Antigen ◽  
Human T Lymphocytes ◽  
Normal Human ◽  
Proliferating Cell

Abstract The proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and appears to be needed for both DNA synthesis and DNA repair. It is present in low amount in resting normal human T lymphocytes and, upon mitogenic stimulation with phorbol dibutyrate and ionomycin, begins to increase in mid-G1 phase, approximately 12 to 15 hours before entry into S phase. PCNA continues to increase in amount throughout the cell cycle and remains high in proliferating cultures. PCNA was extracted from activated normal T cells and from the transformed T-lymphoblastoid cell line Jurkat by a method that recovered approximately 98% of total cellular PCNA but yet retained its associations with other proteins. PCNA immunoprecipitates possessed H1 histone kinase activity, which increased in parallel with increasing cellular content of PCNA. Both the cdc2 and cdk2 kinases were found associated with PCNA in normal T cells, in amounts consistent with detected kinase activity. The results indicate that PCNA is not an inhibitory molecule of cdk/cyclin activity. Both normal and transformed T cells contained PCNA in association with cdk2, cdk4, cdk5, and cdk6, with the amount of PCNA associated with these molecules increasing in the order listed. Relatively high amounts of PCNA were also found associated with cyclins D2 and D3, the major cyclin partners of cdk6 in T cells. Though detected in normal cells, PCNA/cdc2 complexes were present in exceedingly low amount, if at all, in Jurkat cells. This cell line appeared to contain more of nearly all of the cdk and cyclin molecules analyzed, but there seemed to be little difference in the patterns of association of these molecules with PCNA in the cell line as compared with normal human T cells.

scholarly journals Reduction of Granulocyte-Colony Stimulating Factor Requirement in the Course of Long-Term Treatment for More Than 5 Years in Congenital Neutropenia Patients Harbouring ELANE Mutations

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1399-1399
Author(s):  
Cornelia Zeidler ◽  
Anna Nickel ◽  
Ulrike A.H. Grote ◽  
Sabine Mellor-Heineke ◽  
Karl Welte
Keyword(s):  
Body Weight ◽  
Treatment Duration ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Congenital Neutropenia ◽  
Long Term Treatment ◽  
Stimulating Factor ◽  
Chronic Neutropenia

Abstract Congenital neutropenias include a heterogeneous group of diseases characterized by a decrease in circulating neutrophils and different underlying germ-line gene mutations. Since 1988 recombinant human G-CSF is available for the treatment of severe chronic neutropenia patients. In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections. The Severe Chronic Neutropenia International Registry collects clinical information on patients suffering from severe chronic neutropenia since 1994. 312 of 379 CN and 65 of 79 CyN patients receive long-term G-CSF treatment for a median duration of 8,26 years in CN and 9,37 in CyN. Median G-CSF doses vary by neutropenia subtype and gene mutation. Patients with congenital neutropenia revealing ELANE mutations require the highest G-CSF doses compared to other subtypes (median G-CSF dose 5 µg/kg/day in 88 patients). SCNIR follow-up data suggest that pediatric ELANE-CN patients were maintained at a particular G-CSF dose per kg body weight for longer than expected by the gain of body weight. We therefore analysed the reported yearly G-CSF doses in all treated ELANE-CN patients to evaluate the dose trend: From 88 G-CSF treated patients with ELANE-CN we excluded 16 patients with nonresponse (ANC remained below 0.5 x 109 /L) and partial response (ANC remained between 0.5 and 0.99 x 109 /L). Since the gain of body weight is highest during the first 5 years of life with and 10-fold increase we divided G-CSF good responders by age at G-CSF initiation (0-5 years vs above 6 years) and compared G-CSF doses at the end of the dose finding period with the last dose reported. 51 of the remaining 72 patients started G-CSF treatment between the first and 5th year of life with a median G-CSF treatment duration of 9.76 years. 37 of the 51 patients were treated for at least 5 years. In 21 of the 72 patients G-CSF treatment was initiated after their 10thbirthday with a median follow up of 20.45 years. 19 of the 21 patients were treated for at least 5 years. All patients with a treatment duration of less than 5 years were excluded from further analysis. In ELANE-CN patients with treatment start at an age of 0-5 years the mean G-CSF dose decreased significantly from 13.47 µg/kg/day at the time of ANC-response to 7.96 µg/kg/day at the last report (median G-CSF dose decreased from 6.85 µg/kg/day to 4.42 µg/kg/day) during a treatment duration of at least 5 years. In summary, a significant decrease in the individual G-CSF doses could be observed in ELANE-CN patients who started G-CSF treatment during the first five years of their lives suggesting an age dependent alleviation of the severity of the disease as judged by the response to G-CSF. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association of p72 tyrosine kinase with Stat factors and its activation by interleukin-3, interleukin-6, and granulocyte colony-stimulating factor

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3457-3461 ◽  
Author(s):  
T Matsuda ◽  
T Hirano
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Signal Transduction Pathway ◽  
Oncostatin M ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Tyrosine Kinase Activity ◽  
Interleukin 3 ◽  
Hematopoietic Lineage ◽  
Stimulating Factor

Hematopoietic cytokines, including interleukin-3 (IL-3), IL-6, and granulocyte colony-stimulating factor (G-CSF), induce the proliferation, differentiation, and activation of hematopoietic lineage cells. These cytokines activate the Jak/Stat-mediated signal transduction pathway that is important in the biologic activities of these cytokines. In this study, we showed that hematopoietic cytokines, such as IL-3, IL-6, and G-CSF, all induced tyrosine-phosphorylation of Stat family proteins and Stat-associated 150-kD and 72-kD molecules in hematopoietic lineage cell lines. Furthermore, we showed that the 72-kD molecule had tyrosine kinase activity. The tyrosine kinase activity of the 72-kD molecule was enhanced by the stimulation through an IL-6 signal transducer, gp130, that was shared among the receptors for the IL-6-related cytokine subfamily, such as leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor. Because 72-kD tyrosine kinase was distinct from Syk, Tec, and Btk and coimmunoprecipitated with anti-Stat antiserum, we termed it Stat- associated 72-kD tyrosine kinase (p72sak). p72sak may directly activate Stat family proteins or other signal transducing molecules for IL-3, G- CSF, and the IL-6-related cytokine subfamily.

scholarly journals Proliferative effect of the aqueous extract of Hyptis pectinata on liver regeneration after partial hepatectomy in rats

2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 33-36 ◽  
Author(s):  
Gustavo Barreto Melo ◽  
Renata Lemos Silva ◽  
Valdinaldo Aragão Melo ◽  
Ângelo Roberto Antoniolli ◽  
Paulo Roberto Teixeira Michellone ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Aqueous Extract ◽  
Proliferating Cell Nuclear Antigen ◽  
Serum Enzymes ◽  
Nuclear Antigen ◽  
Proliferative Effect ◽  
Water Administration ◽  
Proliferating Cell ◽  
Hepatic Protection

PURPOSE: This study was carried out to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT and gamma-GT) after 67% partial hepatectomy in rats. METHODS: AST, ALT and gamma-GT, were determined by conventional procedures using a spectrophotometer (Model E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). RESULTS:Oral pretreatment during 4 days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was statistically decreased in comparison to the group submited to distilled water administration. The other enzymes assessed disclosed no difference when all groups were compared. CONCLUSION: The present study shows that the aqueous extract of Hyptis pectinata leaves contains some biological active principles that stimulate liver regeneration at 100 mg/kg and cause slight hepatic protection at 200 mg/kg.

scholarly journals The effect of laser on remanescent liver tissue after 90% hepatectomy in rats

2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 29-32 ◽  
Author(s):  
Alexandre Ferreira Oliveira ◽  
Tiago Castro e Silva ◽  
Ajith Kumar Sankarankutty ◽  
Eduardo Garcia Pacheco ◽  
Juliana Ferreira ◽  
...  
Keyword(s):  
Partial Hepatectomy ◽  
Proliferating Cell Nuclear Antigen ◽  
Proliferative Activity ◽  
Wistar Rats ◽  
Liver Parenchyma ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
Serum Aminotransferases ◽  
Hepatic Injuries ◽  
Proliferating Cell

PURPOSE: To evaluate the effect of laser beam on remanescent liver after partial hepatectomy 90%. METHODS: Wistar rats, (N= 42), were divided into six groups with seven specimens each. The partial hepatectomy (HP) was performed in all animals through exeresis of approximately 90% of the liver parenchyma. The animals from groups HP and Laser application, HPL24, HPL48 and HPL72 undertook laser irradiation carried out through application (dose of 22.5 J/cm²) in five different sites in the remanescent liver. The rats were then sacrificed 24, 48 and 72hours after HP procedure, for the liver regeneration analysis,using the Proliferating Cell Nuclear Antigen (PCNA),and for dosage of serum aminotransferases. RESULTS: Were demonstrated an increase of the serum levels of alanine aminotransferase for the group of 24 hours and a decrease for the group of 72 hours exposed to laser. The index of marked cells had a considerable more improvement for the group of 72 hours exposed in laser compared to other groups. CONCLUSION: Laser did not cause hepatic injuries additional to the partial hepatectomy and perhaps led to a benefit by stimulating the proliferative activity.

Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy

1994 ◽  
Vol 39 (2) ◽  
pp. 245-252 ◽  
Author(s):  
Stamatios E. Theocharis ◽  
Antigone S. Skopelitou ◽  
Alexandra P. Margeli ◽  
Kitty J. Pavlaki ◽  
Christos Kittas
Keyword(s):  
Partial Hepatectomy ◽  
Rat Liver ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Regenerating Rat Liver ◽  
Proliferating Cell

scholarly journals Immunohistochemical Study of the Ameliorative Effect of Vitamin E on Liver Regeneration after Different Periods of Partial Hepatectomy

2018 ◽  
Vol 11 (2) ◽  
pp. 661-669
Author(s):  
Mervat M. Halawani ◽  
Gamal S. Abdul Aziz ◽  
Hanan A. Amin ◽  
Hesham N. Mustafa ◽  
Amira A. Elhaggagy
Keyword(s):  
Vitamin E ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Proliferating Cell Nuclear Antigen ◽  
Inhibitory Effect ◽  
Nuclear Antigen ◽  
Albino Rats ◽  
Ameliorative Effect ◽  
Proliferating Cell ◽  
Control Sham

The liver is almost unique in its capacity for regeneration after hepatectomy but the exact mechanisms are not yet fully clarified. Antioxidants have been shown to promote liver regeneration after major hepatectomy. The present study evaluated the ameliorative effect of vitamin E administration on the liver regeneration after different periods of partial hepatectomy (PH) in rats. Fifty-six adult male albino rats were divided into three groups: Control sham operated group; partially hepatectomized group which were divided into three subgroups sacrificed at 1day, 3 days and 7days after the operation respectively; Partially Hepatectomized group with vitamin E pretreatment before PH where the rats were given a daily oral dose of vitamin E until the time of sacrifice of the rats. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and labeling index were demonstrated. After PH, the PCNA positive hepatocytes and the PCNA labeling indices were significantly high after the 1st day and then much decreased after the 3rd day, to be followed by a slight increase at the 7th day. Vitamin E pretreatment in PH rats resulted in a decrease in PCNA positive cells and its labeling indices in the 1st day with a gradual increase in the 3rd and 7th days. Vitamin E has an inhibitory effect in the first 24 hours on liver regeneration followed by stimulatory effect at the third and seventh days after PH. These data indicated that vitamin E pretreatment has an important role in regulation and enhancement of liver regeneration after PH.

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