Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP

Introduction: Thrombocytopenia has been identified as an independent risk factor for retinopathy of prematurity (ROP), although underlying mechanisms are unknown. In this study, the association of platelet count and serum platelet-derived factors with ROP was investigated. Methods: Data for 78 infants born at gestational age (GA) <28 weeks were included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. Results: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p < 0.05–0.001). With adjustment for GA, low platelet counts and low serum concentrations of all 3 factors at PMA 32 weeks were significantly associated with severe ROP. Serum concentrations of all 3 factors also strongly correlated with platelet count (p < 0.001). Conclusion: In this article, we show that ROP, platelet counts, and specific pro-angiogenic factors correlate. These data suggest that platelet-released factors might be involved in the regulation of retinal and systemic angiogenesis after extremely preterm birth. Further investigations are needed.

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Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3

Developmental Neuroscience ◽

10.1159/000516665 ◽

2021 ◽

pp. 1-15

Author(s):

Magnus Gram ◽

Claes Ekström ◽

Bo Holmqvist ◽

Galen Carey ◽

Xiaoyang Wang ◽

...

Keyword(s):

Preterm Birth ◽

Growth Factor ◽

Choroid Plexus ◽

Preterm Infants ◽

Binding Protein ◽

Serum Levels ◽

In Utero ◽

Insulin Like Growth Factor ◽

Extremely Preterm ◽

Extremely Preterm Infants

Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.

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Prevention of Thrombocytopenia and Neutropenia in a Nonhuman Primate Model of Marrow Suppressive Chemotherapy by Combining Pegylated Recombinant Human Megakaryocyte Growth and Development Factor and Recombinant Human Granulocyte Colony-Stimulating Factor

Blood ◽

10.1182/blood.v89.1.155 ◽

1997 ◽

Vol 89 (1) ◽

pp. 155-165 ◽

Cited By ~ 39

Author(s):

Laurence A. Harker ◽

Ulla M. Marzec ◽

Andrew B. Kelly ◽

Ellen Cheung ◽

Aaron Tomer ◽

...

Keyword(s):

Platelet Count ◽

Neutrophil Count ◽

Growth And Development ◽

Granulocyte Colony Stimulating Factor ◽

Serum Concentrations ◽

Colony Stimulating Factor ◽

Platelet Counts ◽

Development Factor ◽

Trough Serum ◽

Stimulating Factor

Abstract This report examines the effects on hematopoietic regeneration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF ) (2.5 μg/kg/d) alone and in combination with recombinant human granulocyte colony stimulating factor (rHu-GCSF ) (10 μg/kg/d) for 21 days in rhesus macaques receiving intense marrow suppression produced by single bolus injections of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia (platelet count <100 × 109/L) was observed between days 12 and 25 (nadir 39 ± 20 × 109/L on day 17), and neutropenia (absolute neutrophil count <1 × 109/L) occurred between days 8 and 30 (nadir 0.167 ± 0.120 × 109/L on day 15). PEG-rHuMGDF (2.5 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.9 ± 0.2 ng/mL and increased the platelet count twofold over basal prechemotherapy levels (856 ± 594 × 109/L v baseline of 416 ± 88 × 109/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was not significantly altered (neutrophil count 0.224 ± 0.112 × 109/L v 0.167 ± 0.120 × 109/L; P < .3). rHu-GCSF (10 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.4 ± 1.1 ng/mL, and reduced the time for the postchemotherapy neutrophil count to attain 1 × 109/L from 22 days to 4 days (P = .005). The postchemotherapy neutropenic nadir was 0.554 ± 0.490 × 109neutrophils/L (P = .3 v hepsulfam-only control of 0.167 ± 0.120 × 109/L). However, thrombocytopenia of <100 × 109 platelets/L was not shortened (persisted from day 12 to day 25), or less severe (nadir of 56 ± 32 × 109 platelets/L on day 14; P = .7 compared with untreated hepsulfam animals). The concurrent administration of rHu-GCSF (10 μg/kg/d) and PEG-rHuMGDF (2.5 μg/kg/d) in four animals resulted in postchemotherapy peripheral platelet counts of 127 ± 85 × 109/L (P = .03 compared with 39 ± 20 × 109/L for untreated hepsulfam alone, and P = .02 compared with 856 ± 594 × 109/L for PEG-rHuMGDF alone), and shortened the period of neutropenia <1 × 109/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing PEG-rHuMGDF to 10 μg/kg/d and maintaining the 21-day schedule of coadministration with rHu-GCSF (10 μg/kg/d) in another four animals produced postchemotherapy platelet counts of 509 ± 459 × 109/L (P < 10−4compared with untreated hepsulfam alone, and P = .04 compared with 2.5 μg/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of either agent. The administration of PEG-rHuMGDF (2.5 μg/kg/d) from day 1 through day 22 and rHu-GCSF (10 μg/kg/d) from day 8 through day 22 in six animals produced peak postchemotherapy platelet counts of 747 ± 317 × 109/L (P < 10−4 compared with untreated hepsulfam alone, and P = .7 compared with PEG-rHuMGDF alone), and maintained the neutrophil count < 3.5 × 109/L (P = .008 v rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow suppression. This improvement in platelet and neutrophil responses by delaying the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of optimizing the dose and schedule of cytokine combinations after severe myelosuppressive chemotherapy.

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Platelet-Derived Growth Factor C in Alcoholics

Alcohol and Alcoholism ◽

10.1093/alcalc/agz094 ◽

2020 ◽

Vol 55 (2) ◽

pp. 157-163 ◽

Cited By ~ 1

Author(s):

C Martín-González ◽

L González-Navarrete ◽

I Ribot-Hernández ◽

V Vera-Delgado ◽

J Alvisa-Negrín ◽

...

Keyword(s):

Multivariate Analysis ◽

Platelet Count ◽

Growth Factor ◽

Serum Levels ◽

Muscle Disease ◽

Platelet Derived Growth Factor ◽

Laboratory Evaluation ◽

Prothrombin Activity ◽

Factor C ◽

Factor Α

Abstract Aims Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics. Methods In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on. Results Serum PDGF levels were significantly lower among patients (675 ± 466 pg/ml) than among controls (1074 ± 337 pg/ml; Z = 3.70; P < 0.001), and even lower among cirrhotics (549 ± 412 among cirrhotics vs 778 ± 487 among non-cirrhotics; Z = 2.33; P = 0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ = 0.50; P < 0.001), platelet count (ρ = 0.44; P < 0.001) and inverse ones with bilirubin (ρ = −0.39; P = 0.002), IL-6 (ρ = −0.33; P = 0.016), IL-8 (ρ = −0.47; P < 0.001), and MDA levels (ρ = −0.44; P < 0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF. Conclusion PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels.

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The Difference between Growth Factor Expression after Single and Multiple Fractures: Preliminary Results in Human Fracture Healing

Disease Markers ◽

10.1155/2015/203136 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Harald Binder ◽

Stefan Eipeldauer ◽

Markus Gregori ◽

Leonard Höchtl-Lee ◽

Anita Thomas ◽

...

Keyword(s):

Growth Factor ◽

Bone Healing ◽

Transforming Growth Factor ◽

Serum Levels ◽

Long Bone ◽

Long Bones ◽

Serum Concentrations ◽

Multiple Fractures ◽

Fracture Group ◽

Significant Difference

Objectives.Circulating levels of VEGF-A (Vascular Endothelia Growth Factor-A), TGF-β1 (Transforming Growth Factor-beta 1), and M-CSF (Macrophage-Colony Stimulating Factor) were found to be predictors of bone healing and therefore prognostic criteria of delayed bone healing or nonunion. The aim of this study was to evaluate a potential rise of these markers in patients with multiple fractures of long bones compared to patients with single fractured long bone.Methods.92 patients were included in the study and finally after excluding all female patients 45 male patients were left for final analysis and divided into the single or multiple fracture group. TGF-β1, M-CSF, and VEGF-A serum levels were analysed over a time period of two weeks.Results.MCSF serum concentrations were higher in the group with multiple fractures as also TGF-β1 serum concentrations were at one and two weeks after trauma. No statistically significant difference was observed in the VEGF-A serum concentrations of both groups at either measurement point.Conclusion.We did observe a correlation between the quantity of the M-CSF and TGF-β1 expressions in serum and the number of fractured bones; surprisingly there was no statistically significant difference in the serum levels between patients with single and multiple fractures of long bones.

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Chronic Peritoneal Dialysis is Associated with Progressive Thrombocytosis

Peritoneal Dialysis International ◽

10.1177/089686088600600207 ◽

1986 ◽

Vol 6 (2) ◽

pp. 71-73 ◽

Cited By ~ 4

Author(s):

Stephen W. Zimmerman

Keyword(s):

Platelet Count ◽

Peritoneal Dialysis ◽

Progressive Increase ◽

Bleeding Tendency ◽

Chronic Peritoneal Dialysis ◽

Thromboembolic Events ◽

Platelet Counts ◽

The Mean ◽

Underlying Mechanisms ◽

The Relationship

The mean platelet count of chronic peritoneal dialysis (cpD) patients (371.000 ± 15.500/mm3) was significantly greater than the mean of hemodialysis (HD) patients (224.000 ± 11.000/mm3. P <. 001). Thrombocvtosis (platelet count > 400.000/ mm3) was noted in 23 of 57 CPD patients hut in only two of 50 chronic HO patients (P < .001). Platelet counts increased with time on CPD. Of CPO patients on dialysis for two years or more .62 % h3d thrombocytosis, in contrast to 6% of HD patients. Platelet counts of CPD patients correlated positivelv with time on PD and serum creatinine. and negatively with age. While there is a progressive increase in platelet counts with peritoneal dialysis. we do not know the underlying mechanisms of thrombocvtosis. the relationship to a possible hypercoagulable state and potential risk for thromboembolic events. The urem1c bleeding tendency 1S associated with abnormal platelet function but platelet counts usually are normal III both uremic patients and those on hemodialysis (1. 2). The bleeding tendency in uremia is corrected by peritoneal dialysis (PD) (3–5), and several have suggested that hypercoagulability may exist in continuous ambulatory peritoneal dialysis (CAPD) (5). However. except tor a rare patient with thrombocytosis (4,6) platelet counts of most PD patients are normal (3–5), although these counts may increase after starting peritoneal dialysis (4). This study was done to assess platelet counts in chronic PD patients and compare them to those on hemodialysis (HD). Platelet counts were elevated in PD when compared to HD and we performed further correlations with clinical and laboratory parameters in PD patients.

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Serum levels of vascular endothelial growth factor in patients with gastrointestinal cancers and correlation with malnutrition, immunosuppression involving MDSC, and systemic inflammation.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.514 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 514-514

Author(s):

Kenji Gonda ◽

Masahiko Shibata ◽

Satoshi Suzuki ◽

Izumi Nakamura ◽

Kensuke Kumamoto ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Healthy Volunteers ◽

Systemic Inflammation ◽

Lymphocyte Count ◽

Serum Levels ◽

Retinol Binding Protein ◽

Vascular Endothelial ◽

Serum Concentrations ◽

Endothelial Growth Factor

514 Background: Vascular endothelial growth factor (VEGF) reportedly plays an important role in the progression of malignant neoplasms, and have been reported to induce myeloid-derived suppressor cells (MDSC) that appears in cancer and inflammation. Methods: Blood samples were collected from 57 patients, including 8 with esophageal cancer, 20 with gastric cancer, 29 with colorectal cancer, and from 18 healthy volunteers. We measured serum concentrations of VEGF and analyzed correlations with nutritional damage, immune suppression and systemic inflammation. As markers of immune function, IL-12 production of PBMC and MDSC (CD 11b+, CD14-, CD33+) were measured. Serum concentrations of albumin and rapid turnover protein were measured as a marker of nutritional status. Results: A significant increase in serum levels was seen in patients with esophageal, gastric, and colorectal cancers compared to healthy volunteers. Levels of VEGF were inversely correlated with serum concentrations of albumin, prealbumin and retinol-binding protein. Serum concentrations of VEGF were inversely correlated with the production of interleukin (IL)-12 and correlated with MDSC. VEGF levels also correlated with neutrophil count and neutrophil/lymphocyte count, and correlated inversely with lymphocyte count. Serum VEGF levels were then divided about a cutoff of 500 pg/ml, with levels of prealbumin and retinol-binding protein significantly decreased in patients with higher VEGF levels. Stimulation index and IL-12 production were significantly decreased in the group with higher VEGF levels, and MDSC counts tended to be higher in this group. Conclusions: These results demonstrated that increased production of VEGF correlated with systemic inflammation, nutritional impairment and inhibition of cell-mediated immunity involving MDSCs. An inactivation of dendritic cells may be occurring by the activation of MDSC. Anti-VEGF therapy may be of importance in treating digestive system cancers.

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Angiogenic Cytokines Are Increased in the Serum of Patients with Waldenastrom’s Macroglobulinemia (WM): Correlations with Clinical Data.

Blood ◽

10.1182/blood.v108.11.5006.5006 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5006-5006

Author(s):

Athanasios Anagnostopoulos ◽

Evangelos Terpos ◽

Konstantinos Zervas ◽

Efstathios Kastritis ◽

Vangelis Eleftherakis-Papaiakovou ◽

...

Keyword(s):

Growth Factor ◽

Clinical Data ◽

Serum Levels ◽

Hematologic Malignancies ◽

Sample Collection ◽

Serum Samples ◽

Symptomatic Disease ◽

Endothelial Growth Factor ◽

Angiogenic Cytokines ◽

Angiopoietin 1

Abstract Angiogenesis is essential step of disease progression in several hematologic malignancies including multiple myeloma (MM). Bone marrow (BM) angiogenesis, assessed by microvessel density (MVD), is increased in 30% of patients with WM and showed only weak correlation with BM infiltration. Two major classes of angiogenic factors, namely the vascular endothelial growth factor (VEGF and mainly its A component (VEGF-A)) and angiopoietins 1 and 2 (Ang-1, Ang-2), has been shown to play pivotal role in tumor angiogenesis. Angiogenin is member of the ribonuclease family, which participates in angiogenesis by influencing the migration and proliferation of endothelial cells. Basic fibroblast growth factor (bFGF) is another cytokine, which is produced by stromal cells and plays significant role in MM pathogenesis. Aim of the study was the evaluation of angiogenesis, as assessed by the measurement of the above angiogenic cytokines, in pts with WM and its correlation with clinical data of the pts. We studied serum samples of 67 pts with serum monoclonal IgM (SMIgM) (44M/23F; median age: 71 years, range: 39–85 years) in various phases of their disease. Fifty-three pts had overt WM (21 untreated, 20 in relapse and 12 in remission). Furthermore, 14 pts with IgM MGUS (N=11) or asymptomatic WM (N=3) were also included. VEGF, VEGF-A, angiogenin, angiopoietin-1 and 2 and bFGF were measured using ELISA methodology (Diaclone, France for VEGF-A and R&D Systems, MN, USA for other cytokines). In all pts, we also evaluated hemoglobin, PLT count, β2-microglobulin (β2m) and albumin levels as well as the presence of splenomegaly, hepatomegaly and lymphadenopathy at the time of sample collection. The same cytokines were also measured in 30 gender- and age-matched controls. All pts with SMIgM had increased serum levels of all cytokines except angiopoietin-1 compared to controls: mean ±SD for VEGF was 299±228 vs. 106±76 pg/ml in pts and controls, respectively (p<0.0001); for VEGF-A 105±102 vs. 6.7±13.6 pg/ml (p<0.0001), for angiogenin 442.9±216.5 ng/ml vs. 239.5±58.5 ng/ml (p<0.0001); for Ang-1 25.1±22 vs. 21±13.5 ng/ml (p=0,4), for Ang-2 3,212±2,110 vs. 1,746±1,023 pg/ml (p=0.0004) and for bFGF 10.2±17.1 vs. 1.3±3.15 pg/ml (p=0.005). However, pts with IgM MGUS or asymptomatic WM (N=14) had elevated values of Ang-1 (40.16±21.66 ng/ml) compared with controls (p=0.002) and pts with symptomatic WM (p=0.003). Pts with active WM (untreated and relapsed) had increased levels of angiogenin compared with asymptomatic WM-MGUS pts and with pts in remission. At the time of sample collection, 16 pts had anemia (Hb<10 g/dl), while 14 pts had increased levels of β2m (>3.5 mg/l), and 11 pts had reduced albumin levels (<3.5 g/dl). Pts with high VEGF-A had higher β2m (r=0.28, p=0.03), high angiogenin was correlated with low albumin (r=−0.39, p=0.001), while high Ang-1 was correlated with low β2m (r=−0.47, p=0.0009) and high Hb levels (r=0.27, p=0.04). Our study suggests that angiogenic cytokines increase in pts with SMIgM supporting a possible paracrine role of these molecules. Ang-1 is the only cytokine which is increased in pts with IgM-MGUS and asymptomatic WM but returns to normal in pts with symptomatic disease. Our results, if confirmed, may provide the basis for clinical trials in WM, which involve anti-angiogenic agents.

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Serum Vascular Endothelial Growth Factor Levels before and after Intravitreous Ranibizumab Injection for Retinopathy of Prematurity

Journal of Ophthalmology ◽

10.1155/2019/2985161 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Xuting Chen ◽

Lin Zhou ◽

Qi Zhang ◽

Yu Xu ◽

Peiquan Zhao ◽

...

Keyword(s):

Growth Factor ◽

Retinopathy Of Prematurity ◽

Systemic Circulation ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Concentrations ◽

Serum Samples ◽

Systemic Complications ◽

Before And After ◽

Endothelial Growth Factor ◽

Vegf Level

Background. Retinopathy of prematurity (ROP) is one of the common complications of prematurity. Intravitreal injection of ranibizumab (IVR), an antivascular endothelial growth factor (VEGF) drug, showed significant benefit for ROP. However, there are concerns about systemic complications of anti-VEGF therapy in preterm infants. Objectives. To evaluate serum VEGF level in the systemic circulation after IVR and the complications associated with IVR for the premature infants with ROP. Methods. This prospective investigation assessed the serum concentrations of VEGF in ROP patients before and after IVR therapy. All the infants had binocular retinopathy and received IVR 0.25 mg per eye as the primary treatment. Serum samples were collected 1 day prior to injection and 1 day, 3 days, and 7 days after IVR treatment. Serum VEGF level was measured by the enzyme-linked immunosorbent assay (ELISA). Results. Fifteen infants (6 girls and 9 boys) were enrolled. The serum concentrations of VEGF 1 day before and 1 day, 3 days, and 7 days after a total of 0.5 mg intravitreal injections of ranibizumab were 226.9 (198.4, 272.4), 12.8 (7.0, 22.4), 16 (12.0, 20.8), and 33.7 (24.0, 48.0) pg/ml, respectively. Serum VEGF levels decreased significantly at 1 day, 3 days, and 7 days after IVR treatment compared with pretreatment concentration (P<0.05). Compared to days 1 and 3 after IVR, serum VEGF level at 7 days after IVR treatment increased significantly (P<0.05). Conclusion. Serum VEGF levels in patients with ROP were suppressed for at least 7 days after IVR treatment. Although the clinical significance of this phenomenon is uncertain, its safety profile requires further investigation.

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Maternal Serum Vascular Endothelial Growth Factor during Early Pregnancy

Clinical Science ◽

10.1042/cs0920567 ◽

1997 ◽

Vol 92 (6) ◽

pp. 567-571 ◽

Cited By ~ 36

Author(s):

Phylip Evans ◽

Timothy Wheeler ◽

Frederick Anthony ◽

Clive Osmond

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Pregnant Women ◽

Serum Levels ◽

Maternal Serum ◽

Interquartile Range ◽

Vascular Endothelial ◽

Serum Concentrations ◽

Serum Progesterone ◽

Endothelial Growth Factor

1. The objectives of the study were: (i) to investigate the serum concentrations of vascular endothelial growth factor (VEGF) in pregnant and non-pregnant women; and (ii) to study the relationship between the levels of maternal serum VEGF and the serum concentrations of human chorionic gonadotrophin (hCG) and progesterone during the first trimester. 2. Total immunoreactive VEGF was measured by competitive RIA using recombinant human VEGF165 and a polyclonal antiserum. Serum VEGF was measured in 60 non-pregnant women of child-bearing age. These data were compared with serum VEGF measured in 363 women between 41 and 91 days of gestation. 3. The median serum VEGF concentration was 1.10 μg/l (interquartile range 0.91–1.30) in the nonpregnant women and 2.13 μg/l (interquartile range 1.62–2.77) in the pregnant women. Serum levels of VEGF were significantly higher among the pregnant cohort (P < 0.0001). Serum VEGF concentration was positively correlated with gestational age, increasing until ten completed weeks of pregnancy. Serum VEGF was negatively correlated with maternal height and weight, and positively correlated with serum hCG and serum progesterone (P ≤ 0.0001 in all cases). Serum VEGF was lower in the pregnant women who smoked (P = 0.06). 4. Our data show a positive and highly significant correlation between maternal serum levels of VEGF and hormones reflecting placental function (hCG, progesterone). We speculate that VEGF production is increased by progesterone and hCG, and that VEGF has a positive influence on trophoblast development. VEGF may also be involved in the initiation of the maternal cardiovascular adaptation to pregnancy.

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Serum levels of cytokines in infants treated with Conbercept for retinopathy of prematurity

10.21203/rs.2.17703/v1 ◽

2019 ◽

Author(s):

Yong Cheng ◽

Xuemei Zhu ◽

Dandan Linghu ◽

Zhongxu Jia ◽

Yongsheng Xu ◽

...

Keyword(s):

Growth Factor ◽

Retinopathy Of Prematurity ◽

Case Series ◽

Serum Levels ◽

Control Group ◽

Serum Concentrations ◽

Term Infants ◽

Inflammatory Protein ◽

Case Series Study ◽

Inducible Protein

Abstract Background: To determine the serum concentrations of cytokines in infants with retinopathy of prematurity (ROP), and to evaluate the changes of serum vascular endothelial growth factor (VEGF) concentration who received intravitreal Conbercept (IVC). Methods: Case series study. Forty infants with ROP treated with IVC 0.25 mg and ten full-term infants with congenital cataract were included. Blood samples were collected before and 1 week, and 4 weeks after IVC. Serum levels of 45 types of cytokines were measured by multiplex bead assay. Results: In the ROP group, significantly higher concentrations of VEGF-A, VEGF-D, macrophage inflammatory protein 1 beta (MIP-1β), interferon-inducible protein-10 (IP-10), regulated on activation, normal T Cell expressed and secreted (RANTES), eotaxin, TNF-α, IL-18, EGF, SCF, PIGF-1, and β-NGF were measured, while lower concentrations of monocyte chemotactic protein-1 (MCP-1) and hepatocyte growth factor (HGF) were observed; when compared with the control group. No significant differences were detected in serum concentrations of VEGF-A and VEGF-D in ROP patients between baseline and 1 week, and 4 weeks after IVC treatment.Conclusion: Besides angiogenic factors, several inflammatory cytokines were associated with ROP. IVC 0.25 mg in ROP patients did not induce circulatory VEGF suppression at 1 week after injection.

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