To use or not to use - IGF for torn PCL /broken Tibia
- 08-04-2006, 03:26 AM
To use or not to use - IGF for torn PCL /broken Tibia
I was wondering if there would be any reason to not use IGF-1 for bone and ligament healing purposes? Would it make much difference in recovery time? Could there be any possible negative sides from using it for this purpose (too quick of repair? repair quickly but not as strong?? ) Just curious cuz i want to heal as fast and as healthily as possible. Also have some M- 4Ohn would this be an appropriate time to use this for joint repair? its been 2 weeks since i had surgery- re-attached my PCL ligament and uncrumbled my Tibia plateau) thanks dudes and dudettes.
- 08-04-2006, 11:33 AM
08-04-2006, 04:04 PM
IGF-1 will heal the bone but not the ligament. For ligament healing you need either GH or VAR or Deca. So VAR & IGF-1 would be my EXTREMELY RECOMMENDED stack for this injury of yours. BIG TIME.
08-04-2006, 07:40 PM
Does anybody know if the methyl-4-oh- nandrolone (m40hn) is similar enough to deca for ligament repair? thanks
08-07-2006, 01:14 AM
What you need is platelet-derived growth factor. I assume you can get this from HGH.
University of North Carolina at Chapel Hill.
Platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor Type 1 have demonstrated chemotactic and mitogenic properties in vitro that could benefit healing ligaments. These growth factors also have demonstrated in vivo effects when used in skin wound-healing models. In a previous study, bFGF and IGF-1, used alone, failed to improve healing. The authors wished to test the hypothesis that platelet-derived growth factor alone or combinations of platelet-derived growth factor plus insulin-like growth factor Type 1, platelet-derived growth factor plus basic fibroblast growth factor, or basic fibroblast growth factor plus insulin-like growth factor Type 1 would increase the healing efficiency of ligaments because of their effects on different parts of the cell replication cycle and their abilities to induce chemotaxis. Ligaments receiving platelet-derived growth factor alone were 73% +/- 55% stronger than their contralateral internal controls (p < 0.0025). Stiffness increased 94% +/- 63% over controls (p < 0.0025), and breaking energy was 101% +/- 104% > controls (p < 0.1). Ligaments treated with a combination of platelet-derived growth factor plus insulin-like growth factor Type 1 and platelet-derived growth factor plus basic fibroblast growth factor also had increases in rupture force, stiffness, and breaking energy over internal controls. Ligaments treated with a combination of basic fibroblast growth factor plus insulin-like growth factor Type 1 also appeared to have some improved healing; the results, however, did not prove to be statistically significant. Synergistic effects of growth factor combinations were not evident.
Department of Orthopaedics, University of California San Diego, La Jolla 92093-0630, USA.
Cellular migration and proliferation are integral aspects of wound healing. An in vitro assay for cellular migration and proliferation using explants of rabbit anterior cruciate and medial collateral ligaments was developed previously. This study presents the effects of serum-free culture medium supplemented with basic fibroblast growth factor, bovine insulin, transforming growth factor-beta 1, and platelet-derived growth factor-B, added either individually or in combination, on cell outgrowth in explants of rabbit anterior cruciate and medial collateral ligaments. Outgrowth was assessed at 3 and 6 days by counting the number of cells surrounding the tissue explants. For explants of both ligaments, cell outgrowth was dependent on the presence of 10% fetal bovine serum or the combination of growth factors. Little outgrowth occurred in explants of either ligament in the presence of basic fibroblast growth factor, transforming growth factor-beta 1, or bovine insulin. Platelet-derived growth factor-B at concentrations of 20 and 100 ng/ml seemed to increase cell outgrowth from medial collateral ligament explants at 6 days. The outgrowth from the explants of both ligaments was much greater in the presence of all four growth factors than the sum of the outgrowth with the individual factors. This synergistic effect was as much as 10-fold and 20-fold for the anterior cruciate ligament explants at days 3 and 6, respectively, but no more than 3-fold for the medial collateral ligament explants at these times. Medial collateral ligament explants exhibited greater cell outgrowth than anterior cruciate ligament explants in 10% serum and in the presence of the four growth factors.
PMID: 7602405 [PubMed - indexed for MEDLINE]
Department of Orthopaedics, University of California San Diego, La Jolla 92093-0630, USA.
Exogenously administered growth factors such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-beta) and basic fibroblast growth factor (bFGF) have been shown to affect connective tissue healing in vivo, but their intrinsic role in the healing response has not been established. In the present study, immunohistochemistry with antibodies directed against these growth factors showed that expression of PDGF, TGF-beta 1 and bFGF was increased in and around the wound site in the rabbit medial collateral ligament (MCL) seven days following surgical injury. The strong expression of PDGF correlated with the observed increased cellularity consistent with this growth factor's mitogenic and chemotactic properties. Expression of these growth factors was also increased in wounded rabbit anterior cruciate ligaments (ACL) at seven days following surgical injury, but such expression was limited to the edge of the ACL injury site and was of lesser intensity relative to the MCL. This study suggests that PDGF and TGF-beta 1, and to a lesser extent bFGF, are actively involved during the early stage of MCL healing, but have a more limited presence in the injured rabbit ACL.
PMID: 9807704 [PubMed - indexed for MEDLINE]
08-07-2006, 01:28 AM
Not sure I understand this one, but maybe some else will get something from it.
Joint Injury and Arthritis Research Group, University of Calgary Health Science Centre, Alberta, Canada.
In this investigation, we demonstrate that cells from normal and healing rabbit ligaments are selective in their responsiveness to various growth factors. The cells analyzed included fibroblasts isolated from the synovium, the anterior cruciate ligament, and the medial collateral ligament (midsubstance and epiligament). Fibroblasts isolated from scar tissue of medial collateral ligament that had been allowed to heal for 3 weeks also were analyzed. The addition of insulin-like growth factor-2 or transforming growth factor-beta 1 was observed to alter, in a dose-dependent manner, the expression of plasminogen activator and plasminogen activator inhibitor by connective tissue cells. However, the response to these growth factors was cell specific. Fibroblasts isolated from the midsubstance, epiligament, and scar tissue of the medial collateral ligament were responsive to these growth factors; fibroblasts isolated from the anterior cruciate ligament and synovium did not have a detectable response. The cells from the normal and healing medial collateral ligament responded to both growth factors by increasing plasminogen activator inhibitor activity. This was observed at both the protein and RNA level. In contrast, the addition of insulin-like growth factor-1 or acidic or basic fibroblast growth factor to cells derived from normal or healing ligament did not result in any detectable alteration of plasminogen activator or plasminogen activator inhibitor activity. These results are similar to those observed with an explant system and indicate that cells isolated from ligament tissue maintain their responsiveness to these growth factors in the absence of matrix. As the major effect of insulin-like growth factor-2 and transforming growth factor-beta 1 on the cells tested was to increase plasminogen activator inhibitor activity, such an alteration should diminish the activity of plasminogen activator, an enzyme capable of directly and indirectly proteolyzing matrix molecules, and thus contribute to a more anabolic environment.
PMID: 7520487 [PubMed - indexed for MEDLINE]
08-07-2006, 01:29 AM
One for dental work with PDGF and IGF-1.
Department of Periodontology, Harvard School of Dental Medicine, Boston, MA.
Two commonly used animal models for evaluating putative periodontal regenerative therapies are the beagle dog model with natural periodontal disease and the non-human primate with ligature-induced attachment loss. The host response, microbiology, and skeletal rates of remodeling of these two models are summarized. In addition, the results of experiments comparing the healing response to periodontal surgery with and without concurrent use of the combination of platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) in these models are presented. At 1 month, PDGF/IGF-I administration resulted in a 64.1% and 51.4% increase in new attachment formation in the non-human primate and canine, respectively, while controls (surgery plus placebo) demonstrated 34.1% and 8.6% increases in new attachment formation in the non-human primate and canine models, respectively. Further, application of PDGF/IGF-I stimulated 21.6% and 65% osseous defect fill in the non-human primate and canine, respectively, while controls demonstrated 8.5% and 14.5% osseous defect fill in the non-human primate and canine, respectively. The osseous response in the canine appears greater than that of the non-human primate, and the new attachment formation was more substantial in the non-human primate than the canine. However, in general these data demonstrate a high degree of consistency in the effects of PDGF/IGF-I in promoting periodontal regeneration. Positive results in these two models--the dog with natural periodontal disease and the non-human primate with ligature-induced attachment loss--justify human clinical trial testing of a putative regenerative therapy.
PMID: 7877089 [PubMed - indexed for MEDLINE]
08-07-2006, 01:33 AM
Kind of gross, but interesting.
Department of Surgery, University of Texas Medical Branch, Galveston, USA.
Many of the anabolic effects of growth hormone (GH) act through insulin-like growth factor-I (IGF-I). Systemic administration of GH in combination with IGF-I has been shown to stimulate wound reepithelialization, however, it causes hyperglycemia or hypoglycemia, respectively. We hypothesize that very low doses of IGF-I in a liposome form will have the same positive wound-healing effect when administered locally as the higher doses of GH plus IGF-I given systemically. To test this hypothesis, rats were given a 40% TBSA full-thickness scald injury and received either placebo IGF-I (5.0 mg/kg/day, subcutaneously), IGF-I liposome (0.9 microgram/kg/week, subcutaneously), or a combination of GH and IGF-I, or IGF-I liposomes for 8 weeks. GH in combination with IGF-I showed a significant increase in postburn weight. Wound reepithelialization, measured by computerized planimetry as percentage original wound area, was significantly increased in rats receiving GH plus IGF-I, GH plus IGF-I liposomes, and IGF-I liposomes when compared to sham, or IGF-I (p < 0.05). Results indicate that small doses of IGF-I, delivered in the form of liposomes, are equally effective in increasing burn wound reepithelialization as the higher doses of GH plus IGF-I, or GH plus IGF-I liposomes.
PMID: 9261692 [PubMed - indexed for MEDLINE]
Shriners Burn Institute, Galveston, TX 77550, USA.
The anabolic effects of growth hormone (GH) in burned patients appear to act both directly and through insulin-like growth factor-1 (IGF-1). We, therefore, hypothesize that exogenous GH plus IGF-1 will attenuate increases in metabolism and lean muscle wasting while promoting wound healing. MATERIALS AND METHODS: Rats, each weighing 440-470 g, were given a 35% total body surface area, full-thickness scald burn and divided into four groups to receive placebo (burned controls), bovine GH (2.5 mg/kg/day), IGF-1 (2.0 mg/kg/day), or bovine GH plus rhIGF-1 (2.5 + 2.0 mg/kg/day), respectively, for 8 weeks. RESULTS: Total body weight gain after 8 weeks averaged 110 g for GH plus IGF-1 compared with gains of 49 and 11 g for GH or IGF-1 alone, respectively. Burned controls lost 24 g. Metabolic rates were significantly reduced in all groups receiving growth hormones. Gastrocnemius muscle dry weight was significantly increased in those receiving GH plus IGF-1 compared with GH and IGF-1 alone or burned controls (p < .01). CONCLUSIONS: Data show that GH plus IGF-1 synergistically increased lean muscle weight, total body weight, and was more effective in re-epithelialization of the burn wound than either GH or IGF-1 alone.
PMID: 8970554 [PubMed - indexed for MEDLINE]
08-07-2006, 01:35 AM
Department of Sports Medicine & Joint Reconstruction Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
BACKGROUND: No studies have been conducted to clarify the in vivo effect of growth factor application on healing in the injured anterior cruciate ligament. HYPOTHESIS: Administration of exogenous growth factors significantly increases the structural properties of the injured anterior cruciate ligament. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty-six rabbits were randomly divided into 4 groups of 9 animals each after an overstretched injury was made in the right anterior cruciate ligament. In group 1, no treatment was applied around the injured anterior cruciate ligament. In group 2, 0.2 mL fibrin sealant was applied around it. In group 3, 4 ng transforming growth factor-beta1 mixed with 0.2 mL fibrin sealant was applied. In group 4, 20 microg platelet-derived growth factor-BB mixed with 0.2 mL fibrin sealant was applied. Each rabbit was sacrificed at 12 weeks after the surgery. In addition, 9 knees randomly harvested from all the left knees were used to obtain normal control data. The femur-anterior cruciate ligament-tibia complex specimens were biomechanically and histologically evaluated. RESULTS: Concerning the maximum load and the stiffness, group 3 was significantly greater than groups 1 and 2, whereas there were no significant differences among groups 1, 2, and 4. Groups 1, 2, 3, and 4 were significantly lower than the control group. CONCLUSIONS: The application of 4 ng transforming growth factor-beta1 significantly enhances healing in the injured anterior cruciate ligament. CLINICAL RELEVANCE: Administration of certain growth factors is of value to be studied as one of the future therapeutic options for the overstretched anterior cruciate ligament injury.
PMID: 15701604 [PubMed - indexed for MEDLINE]
08-07-2006, 01:36 AM
Klinik und Poliklinik fur Strahlentherapie und Radiologische Onkologie, Technische Universitat, Klinikum rechts der Isar, Munchen. [email protected]
BACKGROUND: Current models of radiation myelopathy provide a rationale for growth factor-based prevention strategies. Thus, we tested whether insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) alone or in combination modulate radiation tolerance of the rat cervical spinal cord. MATERIALS AND METHODS: The cervical spinal cord of 68 adult Fisher F344 rats received a total dose of 30-36 Gy, given as a single fraction of 16 Gy followed by a second radiation dose of 14-20 Gy. Continuous intrathecal infusion of bFGF (44 rats) or saline (24 rats) into the cisterna magna was given concomitantly. A further experiment included 14 additional rats which were treated with subcutaneous injection of IGF-1 parallel to irradiation with a total dose of 34 Gy or 36 Gy. 20 rats received combined treatment, i.e. intrathecal infusion of bFGF plus subcutaneous injection of IGF-1, starting 24 hours before irradiation (total dose 33 Gy or 36 Gy) for a total of 4 days. Animals were followed until myelopathy developed or for a maximum of 12 months. Histopathologic examinations were performed post mortem. RESULTS: Treatment with bFGF alone or IGF-1 alone increased the median time to myelopathy significantly. In the 36-Gy group, after combination treatment a comparable prolongation of latency was seen. Moreover, rats treated with 33 Gy and combined bFGF plus IGF-1 showed a significantly reduced risk of myelopathy, too (p = 0.0015, Figures 1 and 2). CONCLUSION: Combination of IGF-1 and bFGF was more potent than single agent treatment. We observed a significantly reduced myelopathy rate at an intermediate radiation dose level and a longer time to myelopathy at a high-dose level. This finding strengthens the evidence that brief therapeutic intervention can decrease radiation-induced neurotoxicity. Further studies will be undertaken to optimize this strategy.
PMID: 11962191 [PubMed - indexed for MEDLINE]
08-07-2006, 01:38 AM
Department of Medicine, United Medical School, St. Thomas's Hospital, London, United Kingdom.
Insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) have both been implicated in the abnormal proliferation of vascular smooth muscle cells (VSMC) that occurs after injury to the arterial wall in vivo. We have investigated the effects of these growth factors on proliferation of rabbit aortic smooth muscle cells (RASMC) in vitro. IGF-I, in contrast to bFGF, is a weak mitogen for RASMC. However, when IGF-I (10 ng/ml) was added in combination with bFGF for 24 h, the effect of the two growth factors on DNA synthesis was synergistic at all concentrations tested (P > 0.001 compared with summed values of bFGF alone plus IGF-I alone), and this synergy was also observed at the level of RASMC proliferation (P < 0.001). Time-course experiments indicated that although bFGF was able to stimulate DNA synthesis after 16 h, activity peaked at 24 h, and a synergistic response with IGF-I was not observed before 24 h. Northern blot analysis demonstrated that IGF-I (10 ng/ml) could selectively upregulate fibroblast growth factor receptor-1 (FGFR-1) mRNA 4.0 +/- 0.24-fold (P < 0.001) without a significant effect on FGFR-2, and this induction in FGFR-1 mRNA occurs in a time- and dose-dependent manner. In addition, IGF-I increases FGFR-1 protein levels in RASMC 2.7 +/- 0.12-fold (P < 0.01), as demonstrated by Western blotting, and this upregulation occurs before the peak in DNA synthesis. These results suggest that IGF-I may be capable of increasing the responsiveness of VSMC to bFGF through modulation of FGFR-1.
PMID: 8967350 [PubMed - indexed for MEDLINE]
08-07-2006, 01:40 AM
Corticosteroid weakens ligaments
Department of Orthopaedics, Brown University School of Medicine, Rhode Island Hospital, Providence 02903, USA.
One hundred and one skeletally mature New Zealand White rabbits were used to study the long-term effects of a single injection of corticosteroid on the biomechanical, histological, and biochemical properties of ligament-healing. Two steroid doses were studied, as previously described. The injections were made into a fascial pocket immediately after transection of the ligament. The animals were killed forty-two and eighty-four days after the injury. In our previous investigation, in which we examined the early (inflammatory and proliferative) phases of ligament-healing, the specimens that had been injected with a dose of steroids equivalent to that given to humans demonstrated significantly inferior biomechanical properties and histological organization relative to controls that had not received an injection. In the current study, we examined the later (remodeling and maturation) phases of ligament-healing and found that the tensile strength (the ultimate stress) of the specimens that had been injected with the steroids returned to a value that was equal to that of the controls that had not received an injection; however, the peak load of the specimens that had been injected with steroids remained inferior to that of the controls. This was accompanied by a lag in the histological maturation.
PMID: 7593077 [PubMed - indexed for MEDLINE]
08-07-2006, 11:42 AM
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