The level of fibroblast growth factor-2 prepared from Advanced Platelet Rich Fibrin (A-PRF) in obese Saudi subjects compared to healthy subjects.

BACKGROUND: The prevalence of obesity has increased substantially in the last few decades. World Health Organization (2020) estimated that around 600 million obese adults worldwide were obese, and a further increase is expected in the future due to increased consumption of high-calorie diets and a sedentary lifestyle as per the evidence. AIM: To evaluate and compare the level of fibroblast growth factor platelet rich fibrin (A-PRF) in obese subject compare to healthy weight subject. METHODS: Blood samples were collected from 23 volunteers, 15 obese subject (test group) and 8 non-obese (control group) at Riyadh Elm University. Considering the smaller sample size of our study, the results are to cautiously be interpreted for generalizability. Studies employing larger sample size are recommended to overcome this point. But considering the meticulous study procedure adhering to the study protocol and set criteria, the study pronounces greater internal validity in the sample chosen. The medical, dental histories, an interview and clinical examination was performed to check the eligibility of the participants to be involved in this study, Blood sample was collected in 10 ml syringe, then being processed using A-PRF centrifugation protocols. Ten milliliters of whole blood without anticoagulant was centrifuged at 1,300 rpm for 14 minutes. RESULTS: The level of FGF-2 released from (A-PRF) concentration was significantly lower on obese which was measured on 4 different times (day 1, day 7, day 14 and day 28), compared to healthy. CONCLUSIONS: There was decrease in FGF-2 level released from (A-PRF) from obese compared to healthy.

Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds.

BACKGROUND: Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. METHODS: Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. RESULTS: All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. CONCLUSION: This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

Low Endogenous Fibroblast Growth Factor 2 Levels Are Associated With Heightened Conditioned Fear Expression in Rats and Humans.

BACKGROUND: Hippocampal concentrations of the neurotrophic factor fibroblast growth factor 2 (FGF2) are negatively associated with the expression of fear following conditioning in rats. Heightened conditioned fear expression may be a prospective risk factor for the development of human anxiety and trauma disorders. However, the relationship between conditioned fear expression and FGF2 is yet to be established in humans. METHODS: Using a cross-species approach, we first investigated the relationship between serum concentrations of FGF2 and individual differences in conditioned fear expression in rats (n = 19). We then subjected 88 human participants, who were recruited from university and community advertisements, to a differential fear conditioning procedure and assessed the relationship between salivary concentrations of FGF2 and fear expression to a conditioned stimulus (CS) (a stimulus paired with a shock) and a CS that was never paired with shock. RESULTS: Rats with low serum levels of FGF2 exhibited significantly more freezing than rats with high serum levels of FGF2. Similarly, relative to those with high salivary FGF2, human participants with low salivary FGF2 exhibited significantly heightened skin conductance responses to the CS without shock during fear conditioning and to both the CS with shock and CS without shock during fear recall. CONCLUSIONS: These studies establish that peripheral markers of FGF2 concentrations are negatively associated with fear expression in both rats and humans. To the extent that conditioned fear expression predicts anxiety and trauma disorder vulnerability, FGF2 may be a clinically useful biomarker in the prediction and eventual prevention of these disorders.

Salivary and serum interleukin 6 and basic fibroblast growth factor levels in patients with oral squamous cell carcinoma.

AIM: A role of various cytokines has been implicated in the pathogenesis of many carcinomas, and albeit the role of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) in sera has been studied in patients with oral carcinomas, data upon salivary IL-6 and bFGF are lacking. The aim of this study was to evaluate levels of IL-6 and bFGF in the saliva and serum of patients with oral squamous cell carcinoma. METHODS: Salivary and serum IL-6 and bFGF were evaluated in a group of 33 patients (28 men, 5 women) with oral squamous cell carcinoma (OSCC), age range 40-73 years , mean 54.05 years. Control group consisted of 23 healhy participants, mean age 25 years. RESULTS: Serum IL-6 and bFGF levels were not significantly different between patients with OSCC and healthy controls. Elevated levels of salivary IL-6 and bFGF in patients with OSCC when compared to the healthy controls were found (p<0.001). CONCLUSIONS: The conclusion is drawn that higher levels of salivary IL-6 and bFGF in patients with OSCC might originate from the local production, probably from carcinoma cells.

ECOG phase II trial of graded-dose peginterferon α-2b in patients with metastatic melanoma overexpressing basic fibroblast growth factor (E2602).

PURPOSE: We investigated the use of graded-dose peginterferon α-2b (Peg-IFN) in patients with stage IV melanoma overexpressing basic fibroblast growth factor (FGF-2). The primary objective was suppression of plasma FGF-2 to within reference range (≤ 7.5 pg/mL). EXPERIMENTAL DESIGN: Plasma FGF-2 was measured at baseline (step 1), and patients with concentrations of 15 pg/mL or more were eligible for study treatment (step 2). Peg-IFN was given weekly at a starting dose of 0.5 µg/kg/wk with increment every 3 weeks based on serial FGF-2 concentrations. RESULTS: Two hundred seven patients entered step 1; 45 (22%) overexpressed FGF-2 (median = 22 pg/dL). Twenty-nine eligible patients entered step 2 and received treatment. Patients' median age was 64 years (range, 29-84 years). Most had more than two prior therapies. FGF-2 decreased in 28 (97%) patients, with suppression to reference range in 10 (35%). Median time to FGF-2 suppression was 30 days. The best clinical responses were partial response (7%) and stable disease (17%). Median progression-free survival (PFS) and overall survival (OS) were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2 suppression were more likely than those who did not to have a response or stable disease (P = 0.03). VEGF concentrations decreased in 27 patients (93%) during treatment and paralleled those of FGF-2 over time. We found no compensatory increase in VEGF among those with FGF-2 suppression. CONCLUSIONS: Graded-dose Peg-IFN suppresses FGF-2 in patients with metastatic melanoma who overexpress FGF-2. Over one third of patients had complete suppression of plasma FGF-2, which correlated with clinical response to this therapy.

The evaluation of basic fibroblast growth factor and fibroblastic growth factor receptor 1 levels in saliva and serum of patients with salivary gland tumor.

Basic fibroblast growth factor (FGF2) is a well-known endothelial mitogen that regulates endothelial cell proliferation, migration, differentiation, and survival. In the present study, we investigated the levels of FGF2 and fibroblastic growth factor receptor 1 (FGFR1) in saliva and serum of patients with salivary gland tumors. Saliva and serum samples were collected from 43 patients with salivary gland tumors and 40 healthy volunteers. The FGF2 and FGFR1 concentrations in saliva and serum samples were measured by enzyme-linked immunosorbent assay. We found that the levels of FGF2 and FGFR1 in saliva and serum from patients with salivary gland tumors were significantly higher than those from healthy control subjects. These results suggest that salivary FGF2 and FGFR1 can be used as potential biomarkers in the diagnosis of salivary gland tumors.

Inflammation markers in healthy and periodontitis patients: a preliminary data screening.

Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.

A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel: an initial report of the phase I-IIa study.

BACKGROUND: Limb ischemia remains a challenge. To overcome shortcomings or limitations of gene therapy or cell transplantation, a sustained release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel has been developed. METHODS AND RESULTS: A phase I-IIa study was performed, in which 7 patients had critical limb ischemia. They were intramuscularly injected with 200 microg of bFGF-incorporated gelatin hydrogel microspheres into the gastrocnemius of the ischemic limb. End-points were safety and feasibility of treatment after 4 and 24 weeks. One patient was excluded from the study for social reasons, but only after symptomatic improvements. In the evaluation of the other 6 patients, significant improvements were observed in the distance walked in 6 min (295+/-42 m vs 491+/-85 m for pretreatment vs after 24 weeks, p=0.023) and in transcutaneous oxygen pressure (53.5+/-5.2 mmHg vs 65.5+/-4.0 mmHg, p=0.03). The rest pain scale also improved (3.5+/-0.2 vs 1.0+/-0.6, p=0.022). The ankle-brachial pressure index improved at 4 weeks but not at 24 weeks. Among 5 patients who had a non-healing foot ulcer, the ulcer was completely healed in 3 patients, reduced in 1, and there was no change in 1 patient at 24 weeks. The blood levels of bFGF were undetected or within the normal level in all patients. CONCLUSIONS: The sustained release of bFGF from gelatin hydrogel might be simple, safe, and effective to achieve therapeutic angiogenesis because it did not need genetic materials or collection of implanted cells, and because it did not have any general effects, which was supported by there being no elevation of the bFGF serum level.

[Influence of V.A.C.-therapy on cytokines and growth factors in traumatic wounds]. / Einfluss der V.A.C.-Therapie auf Zytokine und Wachstumsfaktoren in Traumatischen Wunden.

OBJECTIVE: Clinical observations have shown an accelerated wound healing in wounds of patients treated by Vacuum Assisted Closure (V.A.C.)-therapy. The mechanisms of improved wound healing on cellular level have been hitherto less investigated. In this study the levels of proinflammatory interleukins (IL-6, IL-8, IL-10) and growth factors (VEGF, FGF-2) in serum and wound were monitored. METHODS: The study included 21 patients with traumatic wounds that could not be closed during the first surgical intervention. The soft tissue defects (n = 21) were closed temporarily by Epigard. During the first second-look operation after 2.0 +/- 0.2 days in an average, Epigard was used for another 2.5 +/- 0.4 days as temporary soft tissue coverage in 13 patients (group A). In the remaining 8 patients the wound conditioning was done by V.A.C.(R) for 2.4 +/- 0.3 days (group B). A total of 428 samples of serum and wound fluid samples were collected during the first and second look operation. Levels of IL-6, IL-8, IL-10, VEGF and FGF were measured specific by ELISA. RESULTS: In all interleukins and growth factors there were significant lower serum level concentrations compared with those in wound fluids. During the first temporary dressing change after wound coverage with Epigard the wound samples showed the following levels [Mean (SEM)]: IL-6 49 816 (19 889) pg/ml, IL-8 54 (16) ng/ml, IL-10 314 (44) pg/ml, VEGF 4 746 (766) pg/ml, FGF-2 494 (89) pg/ml. During the second dressing changes we monitored the following levels in group A: IL-6 7 218 (2 542) pg/ml, IL-8 69 (27) ng/ml, IL-10 261 (58) pg/ml, VEGF 3 551 (661) pg/ml, FGF-2 355 (67) pg/ml. In group B the samples of the wound fluid showed the following results: IL-6 16 966 (4 124) pg/ml [p = 0.02], IL-8 223 (91) ng/ml [p = 0.03], IL-10 233 (76) pg/ml [p = 0.38], VEGF 7 490 (1 565) pg/ml [p = 0.01], FGF-2 352 (43) pg/ml [p = 0.48]. CONCLUSION: The increased local release of IL-6, IL-8 and VEGF in wounds after V.A.C.-therapy may be involved in the accumulation of neutrophil granulocytes and angiogenesis, which seams to play a crucial role for the accelerated granulation tissue formation after V.A.C.-therapy compared to wounds treated by Epigard.

Effects of bFGF incorporated into a gelatin sheet on wound healing.

Basic fibroblast growth factor (bFGF) is well known to promote the proliferation of almost all cells associated with wound healing. However, as the activation duration of bFGF is very short in vivo, we incorporated bFGF into an acidic gelatin hydrogel and studied the sustained release of bFGF in vivo. In addition, we investigated the effects of the acidic gelatin sheet containing bFGF on wound healing. To distinguish wound contraction from neoepithelialization, we measured both the wound area and neoepithelium length. Other histological parameters such as thickness of granulation tissue and number of capillaries were also determined as indices of wound healing. Fibrous tissue was assessed using an Elastica van Gieson and Azan stain. A skin defect (1.5 x 1.5 cm) of full thickness was created on the back of each test mouse and the wound was covered with an acidic gelatin hydrogel, referred to as a gelatin sheet in this study (2 x 2 cm), with bFGF (100 microg/site) (A) or without bFGF (B). 1, 2, 3, 5, 7 and 14 days after covering, mice were killed and an enzyme-linked immunosorbent assay (ELISA) was performed to estimate the concentration of bFGF in the plasma. In another experiment, each wound was covered with (A), (B) or a hydrogel dressing (control group, C) and the wound area was measured 1 or 2 weeks postoperatively with a computer planimeter. The histological parameters, as mentioned above, were assessed using a light microscope. Sustained release of bFGF from the gelatin sheet was observed and the gelatin sheet containing bFGF promoted neoepithelialization, granulation, neovascularization and wound closure. This gelatin sheet containing bFGF was concluded to be effective for wound healing and promising for clinical use.

Basic fibroblast growth factor production in vitro by macrophages exposed to Dacron and polyglactin 910.

Macrophage activation by implanted blood-contacting biomaterials modulates smooth muscle cell and endothelial cell ingrowth. The present study evaluates the in vitro interactions between Dacron or polyglactin 910 with macrophages derived from rabbits fed either normal or atherogenic diets. Peritoneal macrophages were cultured in the presence or absence (negative controls) of either biomaterial for 7 weeks. Conditioned media was evaluated for mitogenic activity using a rabbit aortic smooth muscle cell bioassay with or without preincubation with neutralizing anti-basic-FGF antibody. Results demonstrated increased mitogen release from macrophages harvested from the atherosclerotic rabbits. Only macrophages harvested from normal diet fed rabbits increased their mitogen release following exposure to either polyglactin 910 (p < 0.05) or to Dacron (p < 0.005) over controls. The stimulation of mitogen release by polyglactin 910 did not significantly exceed that in response to Dacron. In rabbits fed normal diets neutralization with the anti-basic-FGF antibody inhibited 100% of the Dacron induced mitogen release as compared to 36% of the polyglactin 910 induced mitogen release (p < 0.01). These results demonstrate significant induced mitogen release from macrophages exposed to biomaterials in vitro, much of the smooth muscle cell mitogen represented by basic-FGF.

Increased bFGF level in the serum of patients with phenytoin-induced gingival overgrowth.

To elucidate the involvement of bFGF (basic fibroblast growth factor) in the pathogenesis of phenytoin-induced gingival overgrowth, we measured the concentration of bFGF in the serum of 36 epileptic patients taking phenytoin and in 94 normal volunteers by enzyme-linked immunosorbent assay technique. The concentration of phenytoin in serum was determined by high-performance liquid chromatography. In 34 of 36 patients taking phenytoin in this investigation, apparent gingival overgrowth was noticed. The mean concentration of bFGF was 33.9+/-18.5 pg/ml in the overgrowth group and 10.6+/-5.2 pg/ml in the volunteer group (p<0.01). The serum phenytoin level did not correlate (r=0.22, p=0.2) with the degree of gingival overgrowth but there was a significant correlation (r=0.38, p=0.023) between the degree of gingival overgrowth and the serum bFGF level. However, no correlation was observed among age, daily phenytoin dose, total phenytoin dose, duration of phenytoin therapy, serum phenytoin level, or serum bFGF level. The results suggested that enhanced serum bFGF level was implicated in the pathogenesis of phenytoin-induced gingival overgrowth.