Exposure to Recombinant Human Erythropoietin Increases Survival of Red Blood Cells in Wistar Rats.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5087-5087
Author(s):  
Wojciech Krzyzanski ◽  
Asfiha G Gebreegziabher ◽  
Piotr Kawczak

Abstract Abstract 5087 Purpose The primary goal of this study was to determine if exposure to recombinant human erythropoietin (rHuEPO) increases survival of RBCs in rats. A secondary objective was to test if rHuEPO prolongs survival of RBC by interaction with erythroid progenitor cells or by affecting cells of the reticuloendothelial system. Methods Normal male Wistar rats (337 ± 8 g) were divided into four groups (n=2). Animals in groups 0 and 1 were not treated whereas animals groups 2 and 3 received multiple doses of rHuEPO (Epogen, Amgen, CA) 450 IU/kg three times a week for two weeks via intravenous injections in the tail vein. Subsequently, blood samples (∼ 1-2 mL) were collected from all animals and labeled with water-soluble biotin as a tag for RBC. The biotinylated RBCs were injected back to animals according to the following pattern. Group 1 received blood from Group 2 and Group 2 from Group 1. Animals from Groups 0 and 3 were injected back with their own blood. Two days were allowed for a system equilibration. Next, blood samples (∼ 100 mL) were drawn weekly from each animal until the signal reached the limit of quantification. The biotinylated cells were detected by streptavidin conjugated to phycoerythin and analyzed by flow cytometry (FACSCalibur, Becton-Dickinson). The RBC absolute count was determined by a hematology analyzer (BC-2800 Vet, Mindray, China). The survival data were represented as the fraction of surviving cells. For quantification of RBC survival, the times necessary to reduce the size of the labeled sample by 25, 50, and 75% (T25, T50, and T75) were used. Results The mean survival curves for each group were compared to the control rats (Group 0). The survival curve for animals in Group 3 was distinctly higher that the survival curve for the control which was reflected by the T50 values of 31.5±1.6 and 13.6±0.1 days, respectively. This implies that the survival of RBCs is prolonged by the treatment with rHuEPO. If the effect of erythropoietin on RBC survival is mediated by its interaction with the erythroid progenitor cells, then an increase in the RBC survival in Group 1 is expected. This was somewhat confirmed by the survival curve for Group 1 that was above the control survival curve, however not to the extent of Group 3. Contrary, the survival curve for Group 2 overlapped with the control, supporting the hypothesis that the effect of rHuEPO on RBC survival is not mediated by its interaction with the reticuloendothelial system. The T50 values for Group 1 and 2 were 24.3±7.4 and 15.6±3.0 days, respectively. Conclusions The survival patterns of RBCs following two week long exposure to rHuEPO imply that their lifespan is prolonged when compared to control rats. Lack of an increase of RBC survival for Group 1 and a moderate increase of RBC survival for Group 2 support the endowment hypothesis that rHuEPO prolongs survival of RBCs possible by enhancing viability of the erythroid precursors. Disclosures No relevant conflicts of interest to declare.

2006 ◽  
Vol 14 (4) ◽  
pp. 238-241 ◽  
Author(s):  
Juliane Guimarães de Carvalho ◽  
Rodrigo Cardoso de Oliveira ◽  
Marília Afonso Rabelo Buzalaf

OBJECTIVE: This study evaluated the use of plasma, bone surface (periosteal) and whole bone as biomarkers of chronic fluoride (F) exposure. METHODS: Forty male Wistar rats were assigned to 4 groups (n=10/gr) that differed according to the F concentration they received in the drinking water. Groups 1, 2, 3 and 4 received water containing 0 (control), 5, 15, and 50 mg F/L, respectively. The rats were killed at 120 days of age. Plasma and femur were collected and analyzed for fluoride with the ion specific electrode by the direct method or after hexamethyldisiloxane-facilitated diffusion. Data were tested for statistically significant differences by ANOVA and linear regression (p<0.05). RESULTS: Mean (± SE) plasma F concentrations ranged from 0.030 ± 0.002 to 0.187 ± 0.013 (mg/mL). The concentrations in surface and whole bone ranged from 610 ± 32 to 4,693 222; and 647 ± 22 to 3,439 ± 134 µg/g, respectively. The surface/whole F concentration ratios were 0.941, 1.414, 1.173 and 1.377, for groups 1, 2, 3 and 4 respectively. For plasma and whole bone, the difference among all groups was statistically significant, except for group 2 compared to group 1. For bone surface, all groups differed from each other except for group 2 compared to group 3. A significant positive correlation was found between bone surface and whole bone F (r²=0.94), as well as between plasma and bone surface (r²=0.71) and plasma and whole bone (r²=0.74). CONCLUSIONS: Data suggest that both bone surface and whole bone are suitable biomarkers of chronic F exposure in rats and plasma may be used as indicator of bone fluoride levels.


2018 ◽  
Vol 26 (1) ◽  
pp. 42
Author(s):  
Abdurahman Laqif ◽  
Dewi Kartika DJ Anwar ◽  
Eriana Melinawati

Objectives: To determine the effect of ovarian autotransplan-tation on decreasing FSH level in Wistarrats late menopause model.Materials and Methods: Experimental analytic research on 27 Wistar rats (Rattus novergicus) was divided into 3 groups. Group 1 (K1) or control. Group 2 (K2) performed bilateral oophorec-tomy without autotransplantation. Group 3 (K3) performed bilateral oophorectomy with autotransplantation. Measurements of FSH levels were performed on the first day, day 28 (four weeks after bilateral oophorectomy, during late menopause) and 56 day (four weeks after autotransplant). Measurement of FSH levels using ELISA. Data analysis used ANOVA and Post Hoc test.Results: The mean FSH level measured on day 56 at K1 = 63.400 ng/mL, at K2 = 78.416 ng/mL and K3 = 31.991 ng/mL. There were significant differences between K1 and K2 (p = 0,000), K1 and K3 (p = 0,000), and between K2 and K3 (p = 0,000).Conclusion: Ovarian autotransplantation decrease FSH levels in Wistar rats late menopause model.


2009 ◽  
Vol 24 (2) ◽  
pp. 124-127 ◽  
Author(s):  
Rodrigo Altenfelder Silva ◽  
José Eduardo Rosseto Garotti ◽  
Renata Santos Bittencourt Silva ◽  
Alessandra Navarini ◽  
Adhemar Monteiro Pacheco Jr

PURPOSE: To assess the bactericidal action of ozone pneumoperitonium, and to compare the results with CO2. METHODS: It was used 36 Wistar rats. The animals, under anesthesia, were inoculated with 2ml of E. coli ATCC at a concentration of 10(10)UFC, and 1ml of BaSO4, into the peritoneal cavity. They were divided into three groups: Group 1, CO2 pneumoperitoneum was performed for 15 minutes; Group 2, ozone pneumoperitoneum was performed for 5 minutes at a concentration of 42µg/ml, and Group 3, ozone pneumoperitoneum was performed for 5 minutes at a concentration of 62µg/ml. Six animals from each group were sacrificed after the experiment, and the remaining 6 observed for 24 hours. Material was collected from the cavity of all animals for microbiological study. RESULTS: Ozone presented a greater bactericidal effect than CO2 in those animals sacrificed immediately after pneumoperitoneum. In the animals studied 24 hours after pneumoperitoneum evidenced no difference in bactericidal effect between the two gases. Moreover, no difference in mortality was observed. CONCLUSION: Ozone has a more potent bactericidal effect than carbon dioxide gas, although this did not influence survival of the animals.


2012 ◽  
Vol 27 (12) ◽  
pp. 905-911 ◽  
Author(s):  
Jairo Zacchê de Sá ◽  
José Lamartine de Andrade Aguiar ◽  
Adriana Ferreira Cruz ◽  
Alexandre Ricardo Pereira Schuler ◽  
José Ricardo Alves de Lima ◽  
...  

PURPOSE: To evaluate the effect of local nitroglycerin on the viable area of a prefabricated flap for vascular implant in rats, and to investigate the surgical delay procedure. METHODS: A femoral pedicle was implanted under the skin of the abdominal wall in forty Wistar rats. The animals were divided into four groups of ten: group 1 - without surgical delay procedure and local nitroglycerin; group 2 - with surgical delay procedure, but without local nitroglycerin; group 3 - without surgical delay procedure, but with local nitroglycerin; and group 4 - with simultaneous surgical delay procedure and local nitroglycerin. The percentages of the viable areas, in relation to the total flap, were calculated using AutoCAD R 14. RESULTS: The mean percentage value of the viable area was 8.9% in the group 1. 49.4% in the group 2; 8.4% in the group 3 and 1.1% in the group 4. There was significant difference between groups 1 and 2 (p=0.005), 1 and 4 (p=0.024), 2 and 3 (p=0.003), 2 and 4 (p=0.001). These results support the hypothesis that the closure of the arterial venous channels is responsible for the phenomenon of surgical delay procedure. CONCLUSION: Local nitroglycerin did not cause an increase in the prefabricated viable flap area by vascular implantation and decreased the viable flap area that underwent delay procedures.


2009 ◽  
Vol 52 (4) ◽  
pp. 835-839
Author(s):  
Hugo Juárez Olguín ◽  
Miriam Carrasco Portugal ◽  
Janett Flores Pérez ◽  
Angélica Camacho Vieyra ◽  
Carmen Flores Pérez ◽  
...  

The study analyzed the effect of mannitol on the pharmacokinetics (PK) of amikacin. Adult Wistar rats were treated as follows: Group 1 (G1) received mannitol for three days, Group 2 (G2) received mannitol plus 10 mg/kg of amikacin simultaneously, and Group 3 only amikacin. The PK study was conducted on the 4th day. For which, blood samples were drawn at fixed times during 24 h and immunoenzymatically analyzed. Results revealed significant differences (p<0.05) between the groups, e.g. Cmax were 62.26 ± 15.75 µg/ml for G1, 72.63 ± 24.80 µg/ml for G2 and 68.61 ± 27.40 µg/ml for G3. The AUC also differed in the three groups, being largest for G2, 222.52 ± 47.30 µg/ml/h, and smallest for G1, 135.59 ± 39.00 µg/ml/h. Alteration of the PK parameters observed between the groups must be considered when both drugs are prescribed, although human studies are necessary to confirm the results.


2008 ◽  
Vol 23 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Fredy Corrales ◽  
Marcelo Corrales ◽  
Carlos Cauduro Schirmer

PURPOSE: To compare the effectiveness of intraperitoneally administered vitamin E with the sodium hyaluronate/carboxymethylcellulose membrane (HA/CBMC) in preventing postoperative intraperitoneal adhesion formation. METHODS: Sixty Wistar rats underwent a laparotomy and adhesions were induced (IA). The animals were divided into four groups: group 1, control (IA); group 2 (IA + Vitamin E): group 3 (IA+HA/CBMC) and group 4 (IA+ Vitamin E + HA/CBMC). The Vitamin E (groups 2 and 4) and HA/CBMC (groups 3 and 4) were administered intraperitoneally before the abdominal wall was closed. After 30 days, adhesions were classified by an independent surgeon. RESULTS: Three animals died; one from group 3 and two from group 4. All control animals had substantial adhesions compared with unsubstantial adhesions observed in 11/15 in group 2 (P = 0.000), 11/14 in group 3 (P = 0.001), and 10/13 in group 4 (P = 0.000). CONCLUSION: Vitamin E, administered intraperitoneally, is as effective as HA/CBMC in preventing postoperative adhesions.


Author(s):  
Syed Shoib Md Hussaini ◽  
Akram A Naikwadi ◽  
Narsapur VU

Background: The clinical research in past decade has reported that most second-generation antipsychotics (SGAs) can cause serious metabolic derangement, which substantially increases the risk for type II diabetes mellitus. Several retrospective studies have shown increased in serum triglyceride in patients treated with Clozapine. SGAs induced metabolic syndrome is characterized by weight gain, hyperglycaemia, hypertension, hyperlipidaemia, glucose intolerance and insulin resistance. Metformin is currently used to treat metabolic syndrome and type II diabetes mellitus. It is therefore important to determine whether Metformin is efficacious in treating Clozapine-induced metabolic derangement like dyslipidaemia. Objectives: To evaluate the effect of Metformin in minimizing Clozapine induced metabolic derangement like dyslipidaemia. Methodology: Wistar rats weighing 180-240g either sex were divided into 3 groups of 6 rats each. Group 1 served as control, Group 2 Treated with Clozapine 25mg/kg body weight and Group 3 Treated with Clozapine 25mg + Metformin 100mg/kg body weight for 28 days P.O. Group 2 and group 3 were treated for 28 days. Biochemical investigations: Retro-orbital blood was collected for Lipid profile. Result: Lipid profile of group 2 rats treated with Clozapine showed dyslipidaemia (TG 103.3 ±1.7mg/dl, Tc 113.7 ±1.6mg/dl). Whereas group 3 rats treated with Clozapine 25mg + Metformin showed normal lipid levels (TG 94.7±1.7mg/dl, TC 102.8 ±0.8 mg/dl) comparable to group 1(TG 93.0 ±2.6mg/dl, TC 103.7 ±1.5mg/dl). Conclusion: This study exploring the use of Metformin to prevent metabolic derangement like dyslipidaemias in patients of schizophrenia treated with Clozapine. KEYWORDS: Clozapine; Metformin; Dyslipidaemia.


Author(s):  
Dennis, Amaechi ◽  
E. O. Udosen ◽  
V. S. Ekam ◽  
I. P. Ekpe

Aim: This study aims to determine the effects of methanolic root extract of Holarrehna floribunda on the level of some serum sex hormones, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, progesterone and lipid profile in Wistar rats.   Materials and Methods: Twenty- four male and female Wistar rats (150-250 g body weight) were randomly assigned into 4 groups of 6 rats each. Group 1 (control male) took normal rat chow and drinking water. Group 2 (control female) took normal rat chow and drinking water, Group 3(Male test group), was administered with 200 mg/kg of Holarrehna floribunda extract, Group 4(Female test group), was administered with 200 mg/kg of Holarrehna floribunda. The feeding regimens lasted for 5weeks. Results: The values for the lipid profile shows CHOL in Group 1 and Group 3 were 4.02±0.41 mmol/l  and 5.75±0.09 mmol/l, Group 2 and Group 4 were 3.87±0.22 mmol/l  and 5.80±0.10 mmol/l  respectively, TRIG  for Group 1 and Group 3 were 1.30±0.05 mmol/l  and 2.11±0.15 mmol/l  for Groups 2 and 4 were 1.15±0.03 mmol/l  and (2.10±0.12 mmol/l,HDL-C for Groups 1 and 3 were 30.01±0.82 mg/dL  and 39.88± 1.24mg/dL,for Groups 2 and 4 were 29.98± 0.77 mg/dL  and 38.20± 1.83 mg/dL, LDL-C for Groups 1 and 3 were 2.26±0.37 mmol/L  and 4.17±0.35 mmol/L respectively, for Groups 2 and 4 were 3.27±0.47 mmol/L  and 4.06±0.21 mmol/L  respectively, shows significant increase(p<0.05) in HDL-C (mg/dL) in Groups 1,2,3 and 4.The values obtained showed significant increase (p<0.05) in HDL-C (mg/dL) in Groups 1,2,3and 4The serum concentrations of FSH, Estradiol, LH and progesterone in the control Group 2 were 0.38 ±0.07mIU/mL, 7.83±0.35 mIU/mL, 15.50±0.15 Pg/mL and 0.86±0.03 ng/mL respectively, and in test Group 4 were 0.77±0.04mIU/mL, 8.75±0.17 mIU/mL, 21.09±0.79 Pg/Ml 0.33±0.05 ng/mL. Follicle stimulating hormone levels was significantly higher (p<0.05) in test group compared with control. While in Group 1 and 3, the serum concentrations of FSH, LH, and testosterone in control Group 1 were (0.51 ±0.06) mIU/mL, (16.44±0.31) mIU/mL and (8.41±0.50) ng/mL respectively and in test Group 3 were 0.88±0.06 mIU/mL19.88±1.46mIU/mL and10.68±0.64 ng/mL, respectively. Conclusion: The extract improves the level of sex hormones in both the male and female rats.  which could enhance reproductive functions in normal rats and those with loss of reproductive function.


Author(s):  
Y. Karnakar Reddy ◽  
T. Ramamohan Reddy

In the present investigation it was aimed to evaluate any possible pharmacokinetic interactions between Phenytoin and Rivaroxaban. Study was conducted in Male Wistar rats; animals were divided into three groups. Group 1 received Phenytoin alone, Group 2 received Rivaroxaban alone and Group 3 received Phenytoin and Rivaroxaban concomitantly. The treatment was given for 8 days and the blood samples were collected on day 1 and day 8. The samples were analyzed by HPLC. The results were showed no significant difference in the Pharmacokinetic parameters of Phenytoin in presence of Rivaroxaban. Whereas Rivaroxaban showed significant decrease in both Cmax and tmax in combination with Phenytoin. Phenytoin is a combined-gp inducer and strong CYP3A4 inducer therefore it may induce the metabolism of Rivaroxaban so it reduces the concentrations and increase the elimination rate. Based on the results obtained from pharmacokinetic study it was evident that the single dose of Rivaroxaban in combination with Phenytoin shows statistically significant interactions in its pharmacokinetic parameters.


2009 ◽  
Vol 9 (4) ◽  
pp. 290-295 ◽  
Author(s):  
Nergiz Yılmaz ◽  
Özlem Nisbet ◽  
Cevat Nisbet ◽  
Gözlem Ceylan ◽  
Fatih Hoşgör ◽  
...  

The aim of this study was to describe and quantify the therapeutic value of honey in oral mucosal ulcers healing in comparison with Glyceroloxytriester (TGO). We also aimed to biochemically evaluate the healing effects of honey which had been collected from the Blacksea region flora on mucosal ulcers resulting in material loss.Thirty wistar rats (240±30 g) were enrolled in this study. Excisional wounds were performed in all rats for animal oral mucosal ulcer model. They were randomly allocated to three groups: group 1 was treated with Apitherapeutic agent or honey (0,1 ml, 2x1), group 2 was treated with TGO (0,1ml, 2x1) locally, Group 3 served as the control group.Following the surgical procedure on day 7, biopsy specimens were taken from right buccal mucosa and on day 14 biopsy specimens were taken from left bucal mucosa in all rats. Afterwards, hydroxy pyroline levels were measured. Data were analyzed statisticallyThere was no statistically significant difference between Group 1 and 2, and also between Group 2 and 3, but there was statistically significant difference between Group 1 and 3 on day 7. There was no statistically significant difference between Group 1, 2 and 3 on day 14.


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