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M Laato

Publications and source records attributed to M Laato.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effects of heterodimeric isoform of platelet-derived growth factor PDGF-AB on wound healing in the rat.

Earlier we reported a positive effect of platelet-derived growth factor (PDGF-BB) on rat wound healing while corresponding doses of PDGF-AA were not as effective. The present work was undertaken to study the effects of the heterodimeric form of PDGF (PDGF-AB) on wound healing in rats. Subcutaneously implanted hollow cylindrical cellulose sponges served as an inductive matrix for the granulation tissue. Fifty microliters of solutions containing 0, 5, 50 or 500 ng of PDGF-AB heterodimer were injected daily into the sponges. The analyses of the granulation tissue in the sponge cylinders were carried out 7 days after implantation. Injections of 500 ng of PDGF-AB stimulated significantly the accumulation of collagen and proteins, indicated by the elevated hydroxyproline and nitrogen content of the sponge (+51%, p < 0.01 and +48%, p < 0.001, respectively). Similarly, the amounts of DNA, RNA, hexosamines and uronic acids were significantly higher, reflecting a PDGF-AB-induced increase in the cellularity and glycosaminoglycans. Analyses of wound fluid showed a marked decrease in the number of polymorphonuclear leukocytes in response to PDGF-AB treatment. Injections of a lower dose, 50 ng, of PDGF-AB increased significantly the mean amounts of nitrogen, RNA and uronic acids but no significant changes were observed in other parameters. The lowest dose of PDGF-AB, 5 ng daily, induced no essential effect. In vitro PDGF-AB increased the number of rat granulation tissue-derived fibroblasts and collagen accumulation per culture dish at concentrations of 10 and 30 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat.

Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF-AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA-treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF-AA is effective in vitro but it is clearly less effective in vivo.

Animals↗
PubMed1991

Induced expression of syndecan in healing wounds.

We have studied the expression of an integral cell surface proteoglycan, syndecan, during the healing of cutaneous wounds, using immunohistochemical and in situ hybridization methods. In normal mouse skin, both syndecan antigen and mRNA were found to be expressed exclusively by epidermal and hair follicle cells. After incision and subsequent suturing, remarkably increased amounts of syndecan on the cell surfaces of migrating and proliferating epidermal cells and on hair follicle cells adjacent to wound margins were noted. This increased syndecan expression was shown to be a consequence of greater amounts of syndecan mRNA. Induction was observed already 1 d after wounding, was most significant at the time of intense cell proliferation, and was still observable 14 d after incision. The migrating cells of the leading edge of the epithelium also showed enhanced syndecan expression, although clearly less than that seen in the proliferating epithelium. The merging epithelial cells at the site of incision showed little or no syndecan expression; increased syndecan expression, however, was detected during later epithelial stratification. When wounds were left unsutured, in situ hybridization experiments also revealed scattered syndecan-positive signals in the granulation tissue near the migrating epidermal sheet. By immunohistochemical analysis, positive staining in granulation tissue was observed around vascular endothelial cells in a subpopulation of growing capillaries. Induction of syndecan in granulation tissue both at the protein and mRNA levels was temporally and spatially highly restricted. Granulation tissue, which formed in viscose cellulose sponge cylinders placed under the skin of rats, was also found to produce 3.4 and 2.6 kb mRNA species of syndecan similar to that observed in the normal murine mammary epithelial cell line, NMuMG. These results suggest that syndecan may have a unique and important role as a cell adhesion and a growth factor-binding molecule not only during embryogenesis but also during tissue regeneration in mature tissues.

Animals↗
PubMed1991

Disc degeneration in magnetic resonance imaging. A comparative biochemical, histologic, and radiologic study in cadaver spines.

Magnetic resonance imaging (MRI) findings of 89 autopsied intervertebral discs from 22 cadaveric lumbar spines were correlated with biochemical composition, conventional radiography, and histologic structure to study the nature of disc intensity changes seen in MRI. Discs with a low signal intensity on T2-weighted MRI were characterized by shortening of relaxation times, dehydration, and decreases in total proteoglycan content and chondroitin-keratan sulfate ratios in the nucleus pulposus. This corresponded well with previously published studies. In histologic structure, no obvious differences between MRI findings were found. In conclusion, a low signal intensity in a lumbar disc on T2-weighted MRI probably reflects a true biochemical disc degeneration, but its relation to structural degenerative changes is uncertain. Therefore, MRI seems to be a sensitive and a specific imaging modality for detecting pathologic biochemical disc changes in the spine of a young adult.

Adult↗
PubMed1991

Tumor necrosis factor alpha inhibits wound healing in the rat.

This work was undertaken to study the effects of tumor necrosis factor-alpha (TNF-alpha/cachectin) on developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the two test groups the implants were injected daily for 4 days with a solution containing either 50 or 200 ng of TNF-alpha, while the implants of the control group were treated correspondingly with phosphate-buffered saline solution only. Analyses of granulation tissue and would fluid in the sponge implants were carried out 7, 14 and 21 days after implantation. In histological specimens the ingrowth rate of granulation tissue into the sponge was significantly lower after 7 days in the group treated with 200 ng of TNF-alpha. No such an effect was observed after 14 or 21 days. After 7 days, the mean amounts of nucleic acids reflecting cellularity in the granulation tissue decreased dose-dependently, but nonsignificantly, in the groups treated with TNF-alpha. Simultaneously, the accumulation of collagen hydroxyproline of the sponge was significantly lower in the group treated with 200 ng of TNF-alpha than in the controls (-30%, one-way analysis of variance). This effect was not observed after 14 or 21 days. No significant differences were detected in the amounts of nitrogen, hexosamines and uronic acids between the groups, reflecting unchanged accumulation of glycosaminoglycans in the developing granulation tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Epidermal growth factor (EGF) prevents methylprednisolone-induced inhibition of wound healing.

Subcutaneously implanted cylindrical hollow viscose cellulose sponges were used to study the effect of locally applied epidermal growth factor (EGF) on methylprednisolone-induced inhibition of granulation tissue formation in rats. In in vivo studies the sponges were treated immediately after implantation with a single injection of 2 mg (approximately 1.7 x 10(-3) M) of depot methylprednisolone or with its carrier solution only. Thereafter the implants were injected daily with 5 micrograms of EGF or with its carrier solution 0.1% albumin for 7 days. Methylprednisolone treatment decreased the accumulation of nucleic acids, collagen, and glycosaminoglycans in the developing granulation tissue. After daily injections of EGF the concentrations of these tissue components returned close to the control values. In cultures of rat granulation tissue fibroblasts, 10(-4) M and 10(-3)M methylprednisolone decreased collagen synthesis by 41 and 81% from the control level, respectively. In the presence of methylprednisolone EGF treatment could not increase collagen synthesis of fibroblasts. Methylprednisolone treatment resulted in a dose-dependent reduction in pro alpha 1(I) collagen mRNA levels, which was partially inhibited by low EGF concentrations (1 and 10 ng/ml). In the presence of methylprednisolone all concentrations of EGF increased fibronectin mRNA levels in a dose-dependent manner. It is concluded that EGF treatment can prevent the inhibitory effect of methylprednisolone on wound healing by stimulating fibroblast proliferation but does not stimulate collagen synthesis per cell.

Animals↗
PubMed1988

Interleukin 1 modulates collagen accumulation by rat granulation tissue cells both in vivo and in vitro.

In in vivo studies 0.5 U human interleukin 1 (IL-1) was inoculated daily into a subcutaneously implanted viscose cellulose sponge. IL-1 significantly decreased the dry weight (7.8%) and the hydroxyproline content (24.2%) of granulomas. When the cultured rat granulation tissue cells were exposed to IL-1 (0.5-2.0 U/ml) their collagen production decreased to 80% of that in controls. No effect on cell proliferation was detected.

Animals↗
PubMed1988

Inflammatory reaction and blood flow in experimental wounds inoculated with Staphylococcus aureus.

Wound healing and granulation tissue formation can be accelerated by inoculation with live pathogenic microorganisms. For further elucidation of this phenomenon the present work was undertaken to study the effects of Staphylococcus aureus microorganisms on the inflammatory reaction and blood flow in developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In control animals 1 ml of wound fluid was withdrawn from the central dead space of the implant immediately after implantation and replaced with 1 ml of physiological saline. In experimental animals the implants were injected with live staphylococci, 10(2) or 10(5) microorganisms/ml. Wound fluid was analyzed 3, 7, 10 and 14 days after implantation, whereas measurements of local blood flow and albumin extravasation in the granulation tissue were made after 7 days. Implants inoculated with 10(5) organisms developed infection with pus formation while implants contaminated with 10(2) organisms showed no infection. In wound fluid specimens collected from the infected implants correlation between the number of polymorphonuclear leukocytes and prostaglandin E2 concentration was statistically significant. The most prominent finding in contaminated but uninfected implants was an enhanced local blood flow. This may explain some of the mechanisms leading to S. aureus-induced acceleration of wound healing.

Animals↗
PubMed1988

The effect of epidermal growth factor on granulation tissue formation in the rat.

Subcutaneously implanted cylindrical hollow viscose cellulose sponges were used to investigate the effects of locally applied EGF on developing granulation tissue. The test implants were treated with a single or daily injections of a solution containing 0.2, 1 or 5 micrograms of EGF in 0.1-0.5% albumin while the control implants were treated correspondingly with the carrier solution only. Analyses of wound fluid and granulation tissue in the sponge cylinders were carried out 7 or 10 days after implantation. After daily application of EGF a stimulatory effect on granulation tissue formation was observed: cellularity increased as demonstrated by the elevated amounts of nucleic acids, and the accumulation of collagen and glycosaminoglycans was enhanced. The effect was dose-dependent. After a single application of EGF no essential differences were detected in wound fluid prostaglandin E2 levels or measured components of granulation tissue between the groups. Thus daily application of EGF was necessary to obtain an augmenting effect on granulation tissue formation. EGF seemed to be a potent mitogen for fibroblastic cells released from experimental granulation tissue in a dose-dependent manner. EGF treatment inhibited the production of radioactive hydroxyproline. The decreased rate of collagen synthesis was also indicated by decreased amounts of procollagen mRNAs. In the EGF-treated rats granulation tissue blood flow was significantly higher than that in the control rats 7 days after implantation. In both groups blood flow values of the incision scar region were significantly higher than those of the lumbar skin, but no intergroup differences were detected. In implants injected with EGF the albumin extravasation clearly exceeded that of the control implants. Albumin extravasation in the incision scar region was higher than that in the lumbar skin in both groups. EGF treatment increased procollagen mRNA, particularly at day 4. To study the influence of EGF on methylprednisolone-induced inhibition of granulation tissue formation, the sponge cylinder was injected immediately after implantation with a single dose of 2 mg (approximately equal to 1.7 x 10(-3) M) of depot methylprednisolone. This methylprednisolone injection resulted in a significant fall in the accumulation of nucleic acids, collagen and glycosaminoglycans. After daily injections of EGF these parameters returned to levels close to the control values. In the presence of methylprednisolone EGF could not increase collagen synthesis of fibroblastic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Epidermal growth factor increases collagen production in granulation tissue by stimulation of fibroblast proliferation and not by activation of procollagen genes.

The effects of epidermal growth factor (EGF) on granulation-tissue formation and collagen-gene expression were studied in experimental sponge-induced granulomas in rats. After daily administration of 5 micrograms of EGF into the sponge, total RNA was extracted from the ingrown granulation tissue at days 4 and 7 and analysed by Northern hybridization for the contents of mRNAs for types I and III procollagens. EGF treatment increased procollagen mRNA, particularly at day 4. To determine whether this elevation was due to increased proliferation of collagen-producing fibroblasts or to activation of collagen-gene expression in these cells, fibroblast cultures were started from granulation tissue and treated with EGF. These experiments confirmed that EGF is a potent mitogen for granuloma fibroblasts in a dose-dependent manner. The effect of EGF treatment on radioactive hydroxyproline production in cultured cells was inhibitory. The decreased rate of collagen synthesis was also indicated by decreased amounts of procollagen mRNAs. The results suggest that the stimulation of wound healing and collagen production by EGF is due to increased fibroblast proliferation, and not to increased expression of type I and III procollagen genes.

Animals↗
PubMed1987

Accelerated tissue repair induced by micrococcus varians.

The present investigation was undertaken to study the effect of inoculated Micrococcus varians organisms on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the growth of granulation tissue. The control implants were injected immediately after implantation with 1 milliliter of physiologic saline solution while the experimental implants were injected with a corresponding volume of saline solution containing live micrococci 10(7) microorganisms per milliliter. Cytologic and bacteriologic analyses of wound fluid aspirated from the central dead space of the implants were carried out three, seven and 14 days after implantation. Local blood flow and albumin extravasation were measured on day seven and granulation tissue grown into the implants was analyzed chemically on days seven and 14. No macroscopic infection with pus formation occurred, while Micrococcus varians was cultured from each inoculated implant. In the inoculated implants, the number of wound fluid neutrophils, granulation tissue blood flow and albumin extravasation increased significantly above the control level. Correspondingly, the amounts of granulation tissue deoxyribonucleic acid, nitrogen, collagen hydroxyproline, hexosamines and uronic acids in the inoculated implants exceeded significantly the control value on both days seven and 14. To conclude, inoculation of experimental wounds with nonpathogenic Micrococcus varians organisms enhanced local inflammatory reaction and blood flow, and promoted granulation tissue formation.

Animals↗
PubMed1986

Effect of epidermal growth factor (EGF) on experimental granulation tissue.

Subcutaneously implanted cylindrical hollow viscose cellulose sponges were used to study the effects of locally applied epidermal growth factor (EGF) on developing granulation tissue in rats. In the first set of experiments the test implants were treated with a single injection of a solution containing 5 micrograms of EGF in 0.5% albumin while the control implants were treated correspondingly with the carrier solution only. In the second set of experiments the injections of both test and control implants were repeated daily. Analyses of wound fluid and granulation tissue in the sponge cylinders were carried out 10 days after implantation. After single application of EGF no essential differences were detected in wound fluid prostaglandin E2 levels or various components of granulation tissue between the groups. After daily application, however, a stimulatory effect of EGF on granulation tissue formation was observed: cellularity increased, as evidenced by the elevated amounts of nucleic acids, and accumulation of collagen and glycosaminoglycans was enhanced.

Animals↗
PubMed1986

Effect of a hexosylceramide fraction of the hemodialysate Solcoseryl on wound-healing angiogenesis.

Rabbit ear chambers were used to investigate the effects of a locally applied hexosylceramide fraction (Hex-Cer) of the hemodialysate Solcoseryl on wound-healing angiogenesis. The transparent methacrylate ear chambers were inserted under full aseptic precautions. Immediately after implantation the chambers in control rabbits were filled with physiological saline while the chambers in experimental rabbits were injected with a solution containing either 0.3 or 2.5 micrograms/ml of Hex-Cer, respectively. On the second postoperative day the chambers were reinjected with the corresponding solutions. Thereafter the chambers were examined three times weekly. The onset and rate of the neovascular response were measured by using a standard dissecting microscope equipped with a camera. Vessel growth in ear chambers treated with Hex-Cer at the lower concentration showed very little difference from that seen in control chambers; in both groups the first appearance of new capillaries occurred on an average of 18 days after implantation, and the chambers became fully filled with vessels by the 30th day. However, in chambers treated with Hex-Cer at the higher concentration, the first invasion of capillaries was detected 3 days earlier than in controls (P less than 0.05). Correspondingly, in the chambers treated with Hex-Cer complete vascularization was achieved 7 days earlier than in the control chambers (P less than 0.01). It is concluded that locally applied Hex-Cer exerted an accelerating effect on wound-healing angiogenesis.

Administration, Topical↗
PubMed1986

Stimulation of wound healing by epidermal growth factor. A dose-dependent effect.

This work was undertaken to study the effects of various doses of locally applied epidermal growth factor (EGF) on developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups, the implants were injected daily with a solution containing 0.2, 1, or 5 micrograms of EGF in 0.1% albumin while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders were carried out 7 days after implantation. A stimulatory, dose-dependent effect of EGF on granulation tissue formation was observed: cellularity increased, as evidenced by the elevated amounts of nucleic acids, and accumulation of collagen and glycosaminoglycans was enhanced.

Animals↗
PubMed1986

Effect of a hexosylceramide fraction of the hemodialysate Solcoseryl on experimental granulation tissue.

This work was carried out to study the effects of a hexosylceramide fraction (Hex-Cer) of the hemodialysate Solcoseryl on developing granulation tissue in rats. Subcutaneously implanted cylindrical hollow viscose-cellulose sponges were used as an inductive matrix for the growth of granulation tissue. In the control animals, the implants were treated daily by withdrawing 1 ml of wound fluid from the central dead space of the implant and by injecting back 1 ml of physiological saline. In the experimental animals, the aspirated wound fluid was replaced by a corresponding volume of a solution containing 0.08 microgram of Hex-Cer in physiological saline. Analyses of the wound fluid and granulation tissue were carried out 4, 10 and 21 days after the implantation. Statistically significant increases in the mean amounts of granulation tissue DNA and RNA were observed in the Hex-Cer group as compared with the controls, indicating an augmented cellularity. Concurrently, the mean amounts of collagen hydroxyproline in the Hex-Cer group were significantly higher than the respective control values. Similarly, on days 4 and 10, the amounts of uronic acids were higher in the Hex-Cer group than in the controls, reflecting an enhanced accumulation of glycosaminoglycans. The tissue hemoglobin reflecting the degree of vascularization rose gradually as the healing progressed, the mean amounts being generally higher in the Hex-Cer group than in the controls. Wound fluid pO2, pCO2 and pH as well as wound fluid hemoglobin and lactate concentrations showed no essential differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Actihaemyl↗