Intra-articular injection of rAAV-hFGF-2 ameliorates monosodium iodoacetate-induced osteoarthritis in rats via inhibiting TLR-4 signaling and activating TIMP-1.

Osteoarthritis (OA) is a chronic debilitating degenerative disorder leading to structural, and functional anomaly of the joint. The present study tests the hypothesis that overexpression of the basic fibroblast growth factor (FGF-2) via direct rAAV-mediated gene transfer suppresses monosodium iodoacetate (MIA)-induced knee OA in rats relative to control (reporter rAAV-lacZ vector) gene transfer by intra-articular injection. Rats were treated with 20 µl rAAV-hFGF-2 on weekly basis; on days 7, 14, and 21 after single intra-articular injection of MIA (3 mg/50 µl saline). FGF-2 reduced knee joint swelling and improved motor performance and muscle coordination as evidenced by increased distance travelled, mean speed, rearing frequency in open field test (OFT) as well as fall-off latency in rotarod test together with reduced immobility time in OFT. Moreover, FGF-2 attenuated MIA-related radiological and histological alterations. Indeed, FGF-2 decreased knee joint inflammatory biomarker as demonstrated by reduced mRNA expression of toll like receptor (TLR)-4 and its downstream mediators such as tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß) and high motility group box (HMGB) 1. In parallel, FGF-2 attenuated knee joint degradation biomarkers as reflected by the downregulation of ADAMTS-5 mRNA expression and matrix metalloproteinase 13 (MMP-13) content together with the up-regulation of tissue inhibitor of metalloproteinase (TIMP)-1 mRNA expression. These findings suggest a potential therapeutic role for FGF-2 against MIA-induced knee OA in rats via inhibition of TLR4 signaling and activating TIMP-1, resulting in down-regulation of ADAMTS-5 and MMP-13.

Safety profile of silver sulfadiazine-bFGF-loaded hydrogel for partial thickness burn wounds.

In the present investigation, the safety of novel combinational silver sulfadiazine-bFGF-loaded hydrogel was assured by performing acute skin irritation, sensitization, acute dermal toxicity, and eye irritation in compliance with the Organization for Economic Co-operation and Development guidelines. In the skin irritation study, placebo, test, and positive control (0.8% w/v aqueous solution of formaldehyde) were applied on New Zealand rabbits and monitored for abnormal skin responses including erythema and edema. The placebo and test formulation did not induce any adverse reactions and were classified as nonirritating materials. In the skin sensitization test, guinea pigs were sensitized by positive control (0.1% w/v 1-chloro-2,4-dinitrobenzene in 10% of propylene glycol as a standard skin sensitizing agent), placebo, and test formulations. Weak sensitization was observed in the placebo and test formulation treated groups. Additionally, acute dermal toxicity test was performed in Wistar rats, where no signs of toxicity were observed in biochemical, hematological, and histopathological studies. Moreover, the acute eye irritation test was carried out in rabbits and no abnormal clinical signs were evident in the cornea or iris. As a whole, these findings suggest that the hydrogel formulation does not cause any skin irritation, skin sensitizationand dermal toxic effects, and eye irritation following dermal and ocular applications, respectively. Therefore, all the findings obtained from this preclinical study indicated that this hydrogel formulation is nontoxic and safe for use in animal models.

Facial intramuscular lipoma occurrence following topical cosmetic injection with a mixture of basic fibroblast growth factor: A report of two cases.

Growth factors and cytokines control cell growth, proliferation and differentiation via a network of inter- and intracellular signalling pathways, and are involved in skin self-renewing and wound healing. In recent years, topical and injectable growth factors and cytokines have emerged as an intriguing therapeutic modality that can be harnessed for aesthetic purposes. However, very little data are available on their long-term safety and tolerability. In this report, we describe two cases of patients, who developed intramuscular lipoma of the chin following topical injection with a mixture of basic fibroblast growth factor as the main ingredients for chin augmentation. Biopsies in the two cases were performed at our department, and revealed intramuscular lipoma. Our report indicates that the topical injection of growth factors can lead to tumorigenesis, so health care providers need to be aware of its potential consequences.

Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-µg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.

Preparation and antitumor activity of bFGF-mediated active targeting doxorubicin microbubbles.

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE-PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 µm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.

Fibroblast growth factor 2: Role in prenatal alcohol-induced stimulation of hypothalamic peptide neurons.

Prenatal alcohol exposure (PAE) increases alcohol consumption and risk for alcohol use disorder. This phenomenon in rodents is suggested to involve a stimulatory effect of PAE, in female more than male offspring, on neurogenesis and density of neurons expressing neuropeptides in lateral hypothalamus (LH), including melanin-concentrating hormone (MCH), known to promote alcohol intake. With evidence suggesting a role for fibroblast growth factor 2 (FGF2) and its receptor FGFR1 in stimulating neurogenesis and alcohol drinking, we investigated here whether the FGF2-FGFR1 system is involved in the PAE-induced increase in MCH neurons, in postnatal offspring of pregnant rats given ethanol orally (embryonic day 10-15) at a low-moderate (2 g/kg/day) or high (5 g/kg/day) dose. Our results demonstrate that PAE at the low-moderate but not high dose stimulates FGF2 and FGFR1 gene expression and increases the density of MCH neurons co-expressing FGF2, only in females, but FGFR1 in both sexes. PAE induces this effect in the dorsal but not ventral area of the LH. Further analysis of FGF2 and FGFR1 transcripts within individual MCH neurons reveals an intracellular, sex-dependent effect, with PAE increasing FGF2 transcripts positively related to FGFR1 in the nucleus as well as cytoplasm of females but transcripts only in the cytoplasm of males. Peripheral injection of FGF2 itself (80 µg/kg, s.c.) in pregnant rats mimics these effects of PAE. Together, these results support the involvement of the FGF2-FGFR1 system in mediating the PAE-induced, sex dependent increase in density of MCH neurons, possibly contributing to increased alcohol consumption in the offspring.

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

Intracordal Injection of Basic Fibroblast Growth Factor in 100 Cases of Vocal Fold Atrophy and Scar.

OBJECTIVES/HYPOTHESIS: Vocal fold atrophy, scar, and sulcus reduce the vibratory function of the vocal fold mucosa, which causes severe refractory dysphonia. We have reported encouraging preliminary results using an intracordal injection of basic fibroblast growth factor (bFGF) and showed improvement in phonatory parameters and voice. The present study summarizes our experience with 100 cases of stiffened vocal folds that were treated with bFGF injections. STUDY DESIGN: Retrospective chart review with Interstitial Review Board (IRB) approval. METHODS: Local injection of bFGF was performed in 100 cases of vocal fold pathology, which included 43 cases of vocal fold atrophy, 41 cases with scar, and 16 cases with sulcus. Ten micrograms of bFGF were injected into the vocal folds under topical anesthesia 4 times in each patient. Therapeutic outcomes were examined with maximum phonation time (MPT), voice handicap index-10 (VHI-10), and GRBAS scale. RESULTS: MPT, VHI-10, and GRBAS scores significantly improved in all pathology groups. An improvement on the VHI-10 greater than five points was observed in 82% of atrophy cases, 78% of scar cases, and 67% of sulcus cases. Improvement on the VHI-10 was significantly better in the atrophy group than the scar or sulcus groups. The mild/moderate cases of scar and sulcus showed better improvement than severe cases. CONCLUSIONS: The current large case series indicates positive effects of intracordal injection of bFGF for improvement of voice with no severe adverse events. The effects appeared best for cases of atrophy, while the treatment of severe scar and sulcus requires further improvement. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2059-2064, 2021.

Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer.

Basic fibroblast growth factor (bFGF) has been shown to promote wound healing. The present trial evaluated the clinical efficacy of bFGF for diabetic ulcer, a type of refractory skin ulcer, and the dose-response relationship. This was designed as a randomized, double-blind, dose-ranging, placebo-controlled trial. A total of 150 patients with non-ischaemic diabetic ulcers measuring 900 mm2 or less were randomized into a placebo group (n = 51), a 0.001% bFGF group (n = 49) and a 0.01% bFGF group (n = 50), and 148 of these patients received treatment for 8 weeks or less. The efficacy evaluation was carried out on 139 patients who met the protocol in this trial. The primary outcome was the percentage of patients showing 75% or greater reductions in the area of ulcer. The area of ulcer decreased by 75% or more in 57.5% (27/47), 72.3% (34/47), and 82.2% (37/45) in the placebo, 0.001% bFGF and 0.01% bFGF groups, respectively, and differences were significant between the 0.01% bFGF and placebo groups (p = 0.025). The cure rate was 46.8% (22/47), 57.4% (27/47), and 66.7% (30/45) in the placebo, 0.001% bFGF and 0.01% bFGF groups, respectively. The findings obtained in this trial showed wound healing accelerating effects of bFGF on diabetic ulcers.

Collagen-binding basic fibroblast growth factor improves functional remodeling of scarred endometrium in uterine infertile women: a pilot study.

Intrauterine adhesion (IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2 (bFGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of bFGF 100 µg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients (2-4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved. Histological study showed blood vessel density increased obviously. Three patients (3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the bFGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.

The short- and long-term adverse effects of FGF-2 on tympanic membrane perforations.

SUMMARY: The objective of this study was to investigate the short- and long-term adverse effects of fibroblast growth factor-2 treatment of tympanic membrane perforations. A total of 134 patients with traumatic tympanic membrane perforations were randomly divided into two groups: an observational group and a fibroblast growth factor-2 treatment group. The closure rate, closure time and principal side-effects were compared between the groups at 6 and 12 months. At 6 months, 131 patients were examined to determine healing outcomes and short-term side-effects. The total closure rate differed significantly between the fibroblast growth factor-2 and observational groups (95.5% vs 73.4, p #x003C; 0.01). The fibroblast growth factor-treated group exhibited a significantly shorter closure time than the observational group (11.9±3.1 days vs 52.6 ± 18.1 days, p = 0.00). Three patients with secondary otitis media with effusion, and three with reperforations, were noted in the fibroblast growth factor-2 group. We additionally performed long-term follow-up on 89.1% of the patients in the observational group and 92.5% of the patients in the fibroblast growth factor-2 group; follow-up was performed 16-42 months after perforation closure. Only a small perforation of the pars flaccida developed in the fibroblast growth factor-2 group. No middle ear cholesteatoma was noted in either group. This study suggests that the topical application of fibroblast growth factor-2 to human traumatic tympanic membranes is safe. Otorrhoea was the most common short-term side-effect; other less common side-effects included otitis media with effusion and reperforation. No serious long-term side-effects were found.

Local application of recombinant human fibroblast growth factor-2 on bone repair: a dose-escalation prospective trial on patients with osteotomy.

Based on preclinical evidence in animal models, the present study examined the clinical efficacy and safety of recombinant human fibroblast growth factor-2 (rhFGF-2) to accelerate bone repair in a dose-escalation prospective trial. One of three dosages (200, 400 or 800 microg) of rhFGF-2 in a biodegradable gelatin hydrogel was injected during surgery into the osteotomy site of 59 knee osteoarthritis patients undergoing high tibial osteotomy, and 57 of them were monitored for 16 weeks. The rhFGF-2 dose dependently increased the percentage of patients with radiographic bone union, and decreased the average time needed for such union. The percentages of patients with an absence of pain and full-weight bearing were also greater in the higher dosage groups than in the low dosage group, especially in the clinically critical periods 6, 8, and 10 weeks. Neither blood chemistries nor clinical adverse events were associated with the rhFGF-2 dosages. We therefore conclude that the rhFGF-2 in gelatin hydrogel dose dependently accelerated radiographic bone union of a surgical osteotomy with a safety profile at least at the dosages used, suggesting the clinical efficacy of this agent for bone repair.

Antitumor activity of basic fibroblast growth factor-saporin mitotoxin in vitro and in vivo.

Many cancer cell lines express basic fibroblast growth factor (FGF) receptors, making them potential targets for the delivery of FGF-based cytotoxic compounds. To this end, we have investigated the antitumor activity of a novel mitotoxin, Fibroblast Growth Factor-saporin (FGF-SAP), a conjugate of FGF and the ribosome-inactivating protein, saporin. In vitro, FGF-SAP is cytotoxic for human melanoma, teratocarcinoma, and neuroblastoma cells expressing FGF-receptors. Mice treated with FGF-SAP i.v., on a variety of schedules, showed dramatic tumor growth inhibition with minimal toxicity. Thus, FGF-SAP appears to be a well-tolerated and potent antitumor agent. The potential of FGF-targeted cytotoxicity is discussed.

Delivery strategies to achieve therapeutic myocardial angiogenesis.

The use of recombinant genes or growth factors to enhance myocardial collateral blood vessel function may represent a new approach to the treatment of cardiovascular disease. Proof of concept has been demonstrated in animal models of myocardial ischemia, and clinical trials are underway. Currently, it is unknown which is the safest and most effective delivery strategy to induce clinically important therapeutic angiogenic responses in ischemic myocardium. Most strategies for transcatheter delivery of angiogenic factors have used an intracoronary route, which may have limitations because of imprecise localization of genes or proteins and systemic delivery to noncardiac tissue. The effect of direct intraoperative intramyocardial injection of angiogenic factors on collateral function has been reported in experimental models, and angiogenesis is being studied after direct intramyocardial injection of angiogenic peptides or plasmid vectors during open heart surgery in patients. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without the need for surgery. Intrapericardial delivery of angiogenic factors may offer a theoretical advantage of prolonged exposure of either coronary or myocardial tissue to the administered drug as result of a reservoir function of the pericardium. In this article, we review the different modes of administration for therapeutic myocardial angiogenesis therapy.

Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary.

The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease.

Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial.

BACKGROUND: Single-bolus intracoronary administration of fibroblast growth factor-2 (FGF2) improved symptoms and myocardial function in a phase I, open-label trial in patients with coronary artery disease. We conducted the FGF Initiating RevaScularization Trial (FIRST) to evaluate further the efficacy and safety of recombinant FGF2 (rFGF2). METHODS AND RESULTS: FIRST is a multicenter, randomized, double-blind, placebo-controlled trial of a single intracoronary infusion of rFGF2 at 0, 0.3, 3, or 30 microg/kg (n=337 patients). Efficacy was evaluated at 90 and 180 days by exercise tolerance test, myocardial nuclear perfusion imaging, Seattle Angina Questionnaire, and Short-Form 36 questionnaire. Exercise tolerance was increased at 90 days in all groups and was not significantly different between placebo and FGF-treated groups. rFGF2 reduced angina symptoms as measured by the angina frequency score of the Seattle Angina Questionnaire (overall P=0.035) and the physical component summary scale of the Short-Form 36 (pairwise P=0.033, all FGF groups versus placebo). These differences were more pronounced in highly symptomatic patients (baseline angina frequency score < or =40 or Canadian Cardiovascular Society score of III or IV). None of the differences were significant at 180 days because of continued improvement in the placebo group. Adverse events were similar across all groups, except for hypotension, which occurred with higher frequency in the 30-microg/kg rFGF2 group. CONCLUSIONS: A single intracoronary infusion of rFGF2 does not improve exercise tolerance or myocardial perfusion but does show trends toward symptomatic improvement at 90 (but not 180) days.

Raman imaging demonstrates FGF2-induced craniosynostosis in mouse calvaria.

Craniosynostosis is a severe craniofacial disease where one or more sutures, the fibrous tissue that lies between the cranial bones, fuses prematurely. Some craniosynostosis syndromes are known to be caused by mutations in fibroblast growth factor (FGF) receptors. Mutated FGF receptors are thought to cause constitutive signaling. In this study, heparin acrylic beads released fibroblast growth factor 2 (FGF2) to mimic constitutive signaling by mutated receptors, delivering FGF2 in addition to already existing normal tissue amounts. Fetal day 18.5 mouse sutures were treated with FGF2-soaked beads and cultured in serum free media for 48 h. We have shown previously that this treatment leads to fusion and increased Msx2 expression, but here we use near-infrared Raman imaging to simultaneously examine the mineral components and matrix components of cranial tissue while providing light microscopic spatial information. FGF2-treated mouse sutures show increased v1 phosphate and v1 carbonate bandwidths, indicating a slightly chemically modified mineral being rapidly deposited. In addition, FGF2-treated mouse sutures show a marked increase in mineral-to-matrix ratios compared to control mouse sutures, typical of increased mineralization.

Therapeutic interventions for enhancing collateral development by administration of growth factors: basic principles, early results and potential hazards.

The importance of spontaneously developing collateral vessels to supplement perfusion of tissue rendered ischemic by vascular obstruction was recognized many years ago. However, it was not until potent angiogenesis factors were identified, purified, and produced in sufficient quantities, that the field began its rapid development. In the early 1990s it was first shown that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) proteins could actually stimulate collateral flow. However, additional studies also demonstrated that the duration of exposure of the vessels to angiogenesis factors was critical, and that the administration of proteins, with their relatively brief half-lives, may pose important practical limitations. The demonstration that gene therapy can improve collateral function presents one of the solutions to the conundrum, since gene therapy can be considered a sophisticated form of a sustained delivery system. The results of several clinical trials have been reported. All involve administration of single angiogenesis agents, and most are Phase I trials. The two studies rising to Phase II status demonstrated no treatment effect on the primary end-point. It may therefore be relevant to consider that the molecular mechanisms responsible for angiogenesis are extraordinarily complex, and an optimal angiogenesis intervention may require a 'multiple factor' strategy. It is important to note that no serious side-effects ascribable to an angiogenesis agent were recognized in these trials. However, angiogenesis agents are potent molecules with multiple activities. It is therefore possible that they might occasionally cause side-effects, some serious. Among these, based on their biologic activities, are neovascularization of non-targeted tissues, expansion and induction of instability of atherogenic plaque, and growth of tumors. In summary, there is ample experimental evidence justifying an optimistic outlook relating to our eventually being successful in enhancing collateral flow to ischemic tissue in a clinical setting. However, we are not there yet, and identification of the optimal angiogenesis strategy is still unclear. Additional experimental work, in parallel with large, carefully controlled clinical trials are needed to continue the exciting advances of the last decade, and to achieve the goal of providing patients with alternative potent therapies to improve collateral flow, and thereby to alleviate their symptoms and perhaps to prolong their lives.

Sodium hyaluronate eye drops treatment for superficial corneal abrasion caused by mechanical damage: a randomized clinical trial in the People's Republic of China.

PURPOSE: To evaluate the effectiveness and safety of 0.3% sodium hyaluronate (HA) compared to recombinant bovine basic fibroblast growth factor (rb-bFGF) for the treatment of corneal epithelial abrasion caused by mechanical damage in Chinese patients. METHODS: Thirty patients were randomly assigned to the HA or rb-bFGF treatment group. The HA group was treated with 0.3% HA and 0.5% levofloxacin, and the rb-bFGF group was treated with topical rb-bFGF and 0.5% levofloxacin. The primary endpoint was the clinical effectiveness rates at day 3. Secondary endpoints were the dimensions of the wound area and the percentage of wound closure. RESULTS: After 3 days of treatment, the clinical effectiveness rates of the HA group and the rb-bFGF group were 86.67% (13/15) and 93.33% (14/15), respectively. The dimensions of the wound area were reduced from 9.83±8.50 to 0.02±0.06 mm(2) for the HA group at day 7, and from 10.58±9.94 to 0.02±0.07 mm(2) for the rb-bFGF group. At day 3, the wound closure was almost complete in both groups; 94.73% in the HA group compared to 95.77% in the rb-bFGF group (P>0.05). CONCLUSION: Topical 0.3% HA provided a promising treatment for superficial corneal abrasion caused by mechanical damage in a manner similar to rb-bFGF.

Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris.

We sought to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of basic fibroblast growth factor (bFGF), administered as a single intracoronary injection, to subjects with stable angina pectoris secondary to coronary artery disease. bFGF, an angiogenic growth factor, has been shown to enhance collateral development in animal models of progressive coronary occlusion. To our knowledge, this study represents the initial introduction of parenteral bFGF into humans. This was a phase 1, randomized, dose-escalation trial of bFGF in 25 subjects with coronary artery disease and stable angina. Subjects were randomized 2:1 to a single dose of bFGF or placebo, injected into the left main coronary artery. bFGF doses ranged from 3 to 100 microg/kg, increasing in half-log increments. bFGF was generally well tolerated at doses of 3 to 30 microg/kg. Plasma clearance was 20 +/- 2 ml/kg/min, with an elimination half-life of 85 +/- 11 minutes. bFGF caused acute hypotension ( approximately 10%) that did not appear to be dose-related through the dose range studied. Of the 9 subjects who received 30 to 100 microg/kg bFGF, 2 had sustained hypotension, mild to moderate in severity, lasting 1 to 3 days, and 3 subjects developed bradycardia hours to days after bFGF administration. bFGF dilated epicardial coronary arteries (7.4 +/- 2.5% mean diameter increase, p <0.02). Transient mild thrombocytopenia and proteinuria were observed in some subjects in the 30-microg/kg cohort. No subject had signs suggesting systemic angiogenesis. Thus, intracoronary bFGF, at doses of 3 to 30 microg/kg, was generally well tolerated in subjects with stable angina.