scholarly journals Enhancement of platelet recovery in X-irradiated guinea pigs by romurtide, a synthetic muramyl dipeptide derivative

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2480-2488 ◽  
Author(s):  
K Namba ◽  
T Otani ◽  
Y Osada
Keyword(s):  
Guinea Pigs ◽  
Therapeutic Potential ◽  
Muramyl Dipeptide ◽  
Recovery Phase ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Wbc Count ◽  
Time Required ◽  
Dipeptide Derivative

Abstract The response of megakaryocytes and platelets to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in normal and irradiated guinea pigs. Romurtide was administered subcutaneously in a single dose or daily doses at levels of 1 to 100 micrograms/animal/day to normal animals to assess the dose response. Subsequently, dosage at 100 micrograms/animal/d for 8 consecutive days was initiated in separate groups of animals immediately after 1 Gy total body x-irradiation. In normal animals, a significant dose- dependent increase in the platelet count was noted, and a prolonged thrombocytopoiesis was detectable from 7 through 15 days after the initiation of romurtide administered for 8 days at a dose of 100 micrograms/animal/d. A significant increase in the white blood cell (WBC) count was also observed during days 1 through 11 after beginning romurtide treatment. In the irradiated animals, the treatment with romurtide increased platelet counts during the recovery phase of thrombocytopenia, thus apparently decreasing the time required for recovery to a normal platelet level. Before the rapid recovery of platelet counts by romurtide treatment, a marked increase in the number of megakaryocytes was noted as early as 7 days after irradiation. This increase was accompanied by an accelerated shift of the size distribution of megakaryocytes toward larger size class. Thus, the mean megakaryocyte size was significantly greater in guinea pigs receiving romurtide than in controls. Preceding the increase in the number of megakaryocytes, the serum interleukin-6 levels were found to be approximately 5 times greater than those in control animals. Treatment with romurtide diminished the WBC count nadir, resulting in significantly higher WBC count levels than in controls. Elevation of the plasma fibrinogen level was observed in the treated animals, and normalized gradually after discontinuation of romurtide treatment. These results indicate a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

scholarly journals Enhancement of platelet recovery in X-irradiated guinea pigs by romurtide, a synthetic muramyl dipeptide derivative

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2480-2488
Author(s):  
K Namba ◽  
T Otani ◽  
Y Osada
Keyword(s):  
Guinea Pigs ◽  
Therapeutic Potential ◽  
Muramyl Dipeptide ◽  
Recovery Phase ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Wbc Count ◽  
Time Required ◽  
Dipeptide Derivative

The response of megakaryocytes and platelets to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in normal and irradiated guinea pigs. Romurtide was administered subcutaneously in a single dose or daily doses at levels of 1 to 100 micrograms/animal/day to normal animals to assess the dose response. Subsequently, dosage at 100 micrograms/animal/d for 8 consecutive days was initiated in separate groups of animals immediately after 1 Gy total body x-irradiation. In normal animals, a significant dose- dependent increase in the platelet count was noted, and a prolonged thrombocytopoiesis was detectable from 7 through 15 days after the initiation of romurtide administered for 8 days at a dose of 100 micrograms/animal/d. A significant increase in the white blood cell (WBC) count was also observed during days 1 through 11 after beginning romurtide treatment. In the irradiated animals, the treatment with romurtide increased platelet counts during the recovery phase of thrombocytopenia, thus apparently decreasing the time required for recovery to a normal platelet level. Before the rapid recovery of platelet counts by romurtide treatment, a marked increase in the number of megakaryocytes was noted as early as 7 days after irradiation. This increase was accompanied by an accelerated shift of the size distribution of megakaryocytes toward larger size class. Thus, the mean megakaryocyte size was significantly greater in guinea pigs receiving romurtide than in controls. Preceding the increase in the number of megakaryocytes, the serum interleukin-6 levels were found to be approximately 5 times greater than those in control animals. Treatment with romurtide diminished the WBC count nadir, resulting in significantly higher WBC count levels than in controls. Elevation of the plasma fibrinogen level was observed in the treated animals, and normalized gradually after discontinuation of romurtide treatment. These results indicate a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

scholarly journals Chronic Thrombocytopenia Is Induced in Dogs by Development of Cross-Reacting Antibodies to the MpL Ligand

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3456-3461 ◽  
Author(s):  
David C. Dale ◽  
Janet L. Nichol ◽  
Douglas A. Rich ◽  
Dawn M. Best ◽  
Sherrill J. Slichter ◽  
...  
Keyword(s):  
Essential Role ◽  
High Titer ◽  
In Vivo Model ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Normal Platelet ◽  
The Cross

Abstract The MpL ligand (ML) is a potent stimulus for thrombocytopoiesis. To create an in vivo model of ML deficiency, we injected dogs with a recombinant human ML (rhML) to determine whether cross-reacting antibodies would develop and cause thrombocytopenia. RhML was administered subcutaneously for 8 weeks to three normal dogs (mean platelets, 197 ± 5.5 × 103/μL). Within 5 days their platelet counts were twice baseline and greater than 4 times baseline by day 21. Then, uniformly, chronic thrombocytopenia developed. At 1 week after terminating rhML, mean platelets were 0.5 times baseline and at 2 months 0.25 times baseline. Early in treatment, marrow biopsies showed increased megakaryocyte number and ploidy, which decreased as platelets declined. Paralleling these changes, high titer anti-rhML antibodies developed. Autologous 51Cr-labeled platelet recovery and survival measurements indicated that the thrombocytopenia was principally due to decreased production. Infusion of plasma from the thrombocytopenic dogs into two normal dogs and one dog previously made thrombocytopenic with rhML caused platelet counts to fall gradually. These studies show that dogs with anti-rhML antibodies develop thrombocytopenia, presumably because the cross-reacting antibodies neutralize endogenous canine ML. The results strongly suggest that ML plays an essential role in maintaining normal platelet levels.

Romurtide, a synthetic muramyl dipeptide derivative, accelerates peripheral platelet recovery in nonhuman primate chemotherapy model

Vaccine ◽  
1996 ◽  
Vol 14 (14) ◽  
pp. 1322-1326 ◽  
Author(s):  
Kenji Namba ◽  
Hironobu Nitanai ◽  
Tsuyoshi Otani ◽  
Ichiro Azuma
Keyword(s):  
Nonhuman Primate ◽  
Muramyl Dipeptide ◽  
Platelet Recovery ◽  
Dipeptide Derivative

Use of the Megathrombocyte to Demonstrate Thrombopoietin

1972 ◽  
Vol 28 (01) ◽  
pp. 024-030
Author(s):  
Weiner Marc ◽  
Karpatkin Simon
Keyword(s):  
Platelet Count ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Large Platelet ◽  
Platelet Number ◽  
Lag Period ◽  
Platelet Antibody

SummaryQuantitation of megathrombocyte (large platelet) number was used as an assay for the detection of a humorally-transmitted thrombopoietic stimulus, thrombopoietin. Donor guinea pigs were depleted of circulating platelets by the injection of rabbit anti-guinea pig platelet antibody. Plasma from these donor guinea pigs, when injected into recipient guinea pigs raised their platelet count 1.5 fold and their megathrombocyte number 2.7 fold when compared to plasma injected from donor guinea pigs with normal platelet counts. A lag period of 4 to 5 days preceded the rise in platelet count and megathrombocyte number.

STEM-17. THE GLIOMA STEM CELL PLATELET INTERACTION DRIVES GBM ONCOGENESIS IDENTIFYING A NOVEL THERAPEUTIC APPROACH

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi24-vi24
Author(s):  
Anthony Sloan ◽  
Harry Hoffman ◽  
Peggy Harris ◽  
Christine Lee-Poturalski ◽  
Theresa Elder ◽  
...  
Keyword(s):  
Median Survival ◽  
Therapeutic Approach ◽  
Cancer Metastasis ◽  
Fold Increase ◽  
Cancer Center ◽  
University Hospitals ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Promising Therapeutic Approach ◽  
Transcriptional Pattern

Abstract The effect of platelets on oncogenesis has been studied extensively in cancer metastasis, but not in glioblastoma (GBM), where metastasis is rare. Here we identify the unique crosstalk between glioma stem cells (GSCs) and platelets within GBM solid tumors that enhance disease progression. Targeting GSCs is considered a promising therapeutic approach; however, no clear method has been identified. High platelet counts have been associated with poor clinical outcome in many cancers including ovarian and endometrial cancer. While platelets are known to affect progression of other tumors, mechanisms by which platelets influence GBM oncogenesis are unknown. Immunofluorescence, qPCR, and western blot were used to evaluate the presence of GSCs and platelets and their colocalization in GBM patient tissue at University Hospitals-Seidman Cancer Center. Functional assays followed by RNA sequencing were conducted to determine the functional effect of healthy and GBM platelets on growth of patient derived, autologous GSCs. Our clinical studies suggest elevated platelet counts positively correlate with GSC proliferation and negatively correlate with overall survival in patients with GBM. Patients with high platelet counts ( >350k/µl) had a median survival time of 9 months compared to 16 months median survival for patients with normal platelet count (150-350/µl) (p<0.05). We demonstrate platelet and GSC co-localization in GBM solid tissue and platelet exposure to patient derived GSCs cell lines results in a ≥ 3-fold increase in GSC proliferation compared to GSCs not exposed to platelets (p<0.0005). Similarly we found that platelets increased the self-renewing capacity by enhancing the average sphere size (p < 0.005), and increasing the GSC “Stem-like” transcriptional pattern (P< 0.05). Conversely, pharmacologic inhibition of platelet activation reversed the effect of platelets on GSC proliferation (p ranging from 0.05-0.005). These studies suggests the platelet-GSC interactions appear to stimulate GBM oncogenesis, identifying a potential therapeutic target for the treatment of GBM.

scholarly journals Investigation of Pharmacological Activity of Caralluma penicillata: Anti-Inflammatory Properties and Gastritis Protection against Indomethacin in Adult Guinea Pigs

2014 ◽  
Vol 2014 ◽  
pp. 1-9
Author(s):  
Nabil Albaser ◽  
Najeeb Ghanem ◽  
Mohanad Shehab ◽  
Adnan Al-Adhal ◽  
Mohammed Amood AL-Kamarany
Keyword(s):  
Chronic Inflammation ◽  
Guinea Pigs ◽  
Therapeutic Potential ◽  
Histological Study ◽  
Folk Medicine ◽  
Ethanol Extract ◽  
Optimum Dose ◽  
Repeated Doses ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Caralluma is a plant that possessing a great therapeutic potential in folk medicine in Yemen, namely, Caralluma penicillata (C. penicillata) as antiulcer. The study aims to evaluate the anti-inflammatory properties and gastritis protection activity of C. penicillata against indomethacin in adult guinea pigs. The study was divided into four parts: firstly, the optimum dose of extract as anti-inflammatory effect was determined. Secondly, the acute anti-inflammatory effect of extract were estimated. Thirdly, the repeated doses of extract against chronic inflammation was estimated. The anti-inflammatory activity of extract was compared with indomethacin as a prototype of drug against inflammation. Fourthly, the gastritis protection properties of extract with/without indomethacin were performed. The results showed that a 400 mg/kg of 10% ethanol extract produced the maximum of anti-inflammatory effect. Also, the single dose of extract was equipotent for indomethacin (10 mg/kg), but shorter in duration with regard to acute anti-inflammatory effect. In addition, the repeated doses of extract against chronic inflammation were less potent than indomethacin with regard to ulcerogenic effect. On the other hand, extract-indomethacin combination reduced the gastritis effect of indomethacin based on ulcer index and histological study.

scholarly journals Point-of-care microvolume cytometer measures platelet counts with high accuracy from capillary blood

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256423
Author(s):  
William M. Dickerson ◽  
Rebecca Yu ◽  
Helena U. Westergren ◽  
Jonathan Paraskos ◽  
Philipp Schatz ◽  
...  
Keyword(s):  
Point Of Care ◽  
Venous Blood ◽  
Reference Method ◽  
Time Data ◽  
Platelet Recovery ◽  
Blood Samples ◽  
Impedance Analyzer ◽  
Platelet Counts ◽  
Platelet Antibodies ◽  
Care Assessment

Background Point-of-care (PoC) testing of platelet count (PLT) provides real-time data for rapid decision making. The goal of this study is to evaluate the accuracy and precision of platelet counting using a new microvolume (8 μL), absolute counting, 1.5 kg cytometry-based blood analyzer, the rHEALTH ONE (rHEALTH) in comparison with the International Society of Laboratory Hematology (ISLH) platelet method, which uses a cytometer and an impedance analyzer. Methods Inclusion eligibility were healthy adults (M/F) ages 18–80 for donation of fingerprick and venous blood samples. Samples were from a random N = 31 volunteers from a single U.S. site. Samples were serially diluted to test thrombocytopenic ranges. Interfering substances and conditions were tested, including RBC fragments, platelet fragments, cholesterol, triglycerides, lipids, anti-platelet antibodies, and temperature. Results The concordance between the rHEALTH and ISLH methods had a slope = 1.030 and R2 = 0.9684. The rHEALTH method showed a correlation between capillary and venous blood samples (slope = 0.9514 and R2 = 0.9684). Certain interferents changed platelet recovery: RBC fragments and anti-platelet antibodies with the ISLH method; platelet fragments and anti-platelet antibodies on the rHEALTH; and RBC fragments, platelets fragments, triglycerides and LDL on the clinical impedance analyzer. The rHEALTH’s precision ranged from 3.1–8.0%, and the ISLH from 1.0–10.5%. Conclusions The rHEALTH method provides similar results with the reference method and good correlation between adult capillary and venous blood samples. This demonstrates the ability of the rHEALTH to provide point-of-care assessment of normal and thrombocytopenic platelet counts from fingerprick blood with high precision and limited interferences.

scholarly journals Platelet Decrease and Efficacy of Platelet-Rich Plasma Return for Peripheral Blood Stem Cell Apheresis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Takahiro Shima ◽  
Teppei Sakoda ◽  
Tomoko Henzan ◽  
Yuya Kunisaki ◽  
Takahiro Maeda ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Platelet Count ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Platelet Rich Plasma ◽  
Blood Stem Cell ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Cd34 Cells

Peripheral blood stem cell (PBSC) transplantation is a key treatment option for hematological diseases and widely performed in clinical practice. Platelet loss is the major complication of PBSC apheresis, and platelet-rich plasma (PRP) return is recommended in case of severe platelet decrease following apheresis; however, little is known about the frequency and severity of platelet loss nor the efficacy of PRP return post-apheresis. To address these questions, we assessed changes in platelet counts following PBSC-related apheresis in 270 allogeneic (allo)- and 105 autologous (auto)-PBSC settings. We also evaluated efficacy of PRP transfusion on platelet recovery post-apheresis. Platelet counts reduced up to 70% post-apheresis in both allo- and auto-PBSC settings, while severe platelet count decrease (< 50 x 109/L) was only observed in auto-PBSC patients (Figure 1). We next analyzed the relationship between severe platelet (< 50 x 109/L) after apheresis and several clinical factors by using univariate and multivariate analysis for auto-PBSC patients. As shown in Table 1, in univariate analysis, severe platelet counts following auto-PBSC apheresis was found more frequently in patients with lower platelet count, lower percentage of CD34+ cells in PB at pre-apheresis, repeated round of apheresis, and smaller number of collected CD34+ cells. On the other hand, in multivariate analysis, the white blood cell (WBC) counts pre-apheresis was the only significant risk factor of severe platelet count following apheresis (p = 0.038). We finally analyzed the transitions of platelet counts in the setting of apheresis. The median platelet counts at pre-apheresis, post-apheresis, and post-PRP return were 187.0 x 109/L, 132.0 x 109/L, and 154.0 x 109/L for allo-PBSC apheresis, and 147.0 x 109/L, 111.0 x 109/L, and 127.0 x 109/L for auto-PBSC apheresis (p < 0.0001 for all, allo-PBSC donors and auto-PBSC patients, respectively) (Figure 2), indicating that PRP return post-apheresis facilitated a rapid platelet recovery in both allo- and auto-settings. Collectively, our data suggest that WBC counts pre-apheresis is a useful predictor for severe platelet decrease following auto-PBSC apheresis and that PRP return is an effective mean to facilitate platelet recovery post-apheresis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Microscopic platelet size and morphology in various hematologic disorders

Blood ◽  
1978 ◽  
Vol 51 (3) ◽  
pp. 479-486
Author(s):  
Z Zeigler ◽  
S Murphy ◽  
FH Gardner
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Lupus Erythematosus ◽  
Thrombocytopenic Purpura ◽  
Hematologic Disorders ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Large Size ◽  
Platelet Size ◽  
Microscopic Evaluation ◽  
Size And Morphology

Microscopic evaluation of apparent platelet size and morphology was examined in a variety of hematologic disorders. The time of preparation of the blood smear was important. An artifactual increase in platelet size was noted on blood films from 20 normal individuals that were prepared either immediately or 180 min after venipuncture. The clearest differentiation of patient categories was obtained with smears prepared 60 min after venipuncture using blood anticoagulated with K3EDTA. Under these conditions, normal size and morphology values were found in thrombocytopenic patients with aplasia or with increased splenic pooling. In contrast, large size values were a reliable finding in idiopathic thrombocytopenic purpura patients, whose platelet counts were less than 50,000/microleter. Large size values were also noted in patients with infiltrated bone marrows or myeloproliferative syndromes regardless of the platelet count. The last two groups usually showed abnormal platelet morphology with greater than 10% hypogranular platelets. Normal platelet size and morphology were observed in patients with iron-deficiency and megaloblastic anemias and in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus who had normal platelet counts.

scholarly journals Prolonged thrombocytosis in mice after 5-fluorouracil results from failure to down-regulate megakaryocyte concentration. An experimental model that dissociates regulation of megakaryocyte size and DNA content from megakaryocyte concentration

Blood ◽  
1990 ◽  
Vol 76 (3) ◽  
pp. 508-515 ◽  
Author(s):  
PJ Chenaille ◽  
SA Steward ◽  
RA Ashmun ◽  
CW Jackson
Keyword(s):  
Feedback Control ◽  
Dna Content ◽  
Inverse Relationship ◽  
Feedback Regulation ◽  
Model System ◽  
Feedback Controls ◽  
Platelet Recovery ◽  
Normal Platelet ◽  
Platelet Number ◽  
C3h Mice

Abstract Rodents treated with 150 mg/kg of 5-fluorouracil (5-FU) exhibit a marked and prolonged rebound thrombocytosis, suggesting that feedback control of one or more megakaryocyte characteristics (size, polyploidy, or concentration) is altered. To determine the changes in megakaryocytes that lead to such a profound thrombocytosis, C3H mice were injected with 150 mg/kg 5-FU, and platelet and megakaryocyte responses were examined at frequent intervals from days 1 through 25. After 5-FU injection, all megakaryocyte indices decreased, as did platelet number. However, the decrease in platelets to one third of control was greater than the decreases in megakaryocyte indices, suggesting that thrombocytopoiesis was ineffective from days 3 through 7 post 5-FU. Megakaryocyte size began to recover on day 4, followed by polyploid DNA content on day 5, and megakaryocyte concentration and platelets at 7.5 days. Megakaryocyte size peaked on days 6 through 8 (1.25 x normal), followed by megakaryocyte polyploid DNA content on day 8, megakaryocyte concentration on days 9 through 12 (2 1/2 to 3x normal), and platelets on days 12 through 15 (2x normal). Platelet levels are thought to be important in the feedback regulation of megakaryocytes; however, only polyploid DNA content distributions showed a close inverse relationship to platelet counts during both the recovery and rebound thrombocytosis phases after 5-FU. In contrast, megakaryocyte size peaked before platelet recovery commenced, while megakaryocyte concentration increased in parallel with platelets from 7.5 to 10 days post 5-FU and continued to be maintained at 2 to 3 times normal through day 13, despite platelet levels that were more than twice normal. Both megakaryocyte size and polyploid DNA content distributions shifted toward lower values in response to the rebound thrombocytosis (DNA content on day 10 and size on days 12 and 13). Splenectomy did not substantially alter the pattern of post 5-FU rebound thrombocytosis or megakaryocyte response from that seen in intact mice, indicating that splenic megakaryocytes are not responsible for the prolonged thrombocytosis seen after this drug. In summary, the prolonged thrombocytosis after 5-FU administration results from failure to down-regulate the number of precursors entering the differentiating megakaryocyte compartment. These data indicate that megakaryocyte size and DNA content are responsive to different feedback controls than megakaryocyte concentration in this model system.

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