Skin tightening effects of the ultrapulse CO2 laser.

This study analyzed the skin tightening or contracture effect of the Ultrapulse carbon dioxide (CO2) laser on the skin of hairless guinea pigs by light and electron microscopic, histologic, and tensiometric evaluations. Two 2 X 2 cm squares of back skin were precision tattooed on each of the animals in the study (n = 12). One square served as the control, and the other square was used as experimental skin. The experimental skin was treated with three passes of the CO2 laser at 500 mJ and 5 W using a 3-mm collimated hand-piece. Skin specimens from three animals were analyzed at 1, 4, 8, and 12 weeks. After three passes, the length of the square was reduced by 27 percent, and the width was reduced by 40 percent. Over the next 12 weeks, as the animals grew, the dimensions of the control areas also increased. The laser-treated areas continued to maintain their contracted dimensions, however. By the 12th week, the laser-treated areas were 28.35 percent shorter in length and 15.5 percent shorter in width than the control areas. Histologic examination demonstrated a significantly higher content of collagen in the reticular layer, which was more compact than that of the normal skin. Electron microscopy revealed that the laser had induced shortening of the collagen fibers (7.45 percent; p = 0.026), which persisted beyond the 12th week. Laser treatment did not significantly alter the tensile strength of the skin, although, at the 8th week, the treated areas had a slightly higher tensile strength.

Aberrant external jugular vein phlebectasia with tongue pain.

We have not encountered any other report of phlebectasia with tongue pain in the literature. The pain disappeared after the anomalous venous communication was excised.

Role of growth factors in scar contraction: an in vitro analysis.

Excessive scar contracture by wound fibroblasts can have devastating consequences, ranging from body disfigurement to joint immobility. The ability of fibroblasts isolated from lesions of hypertrophic scars, keloids, normal skin, or normal scars in contracting the provisional wound matrix (i.e., fibrin clot) was compared and analyzed. Hypertrophic scar fibroblasts showed a consistently higher basal level of fibrin matrix gel (FMG) contraction than other fibroblasts. This heightened basal level of contractility may be attributed partially to the autocrine effect of transforming growth factor-beta 1 (TGF-beta 1). Normal and keloid fibroblasts exhibited similar basal rates of FMG contraction, and both responded to platelet-derived growth factor (PDGF) and TGF-beta by increasing FMG contraction two- to threefold. However, 45% of the TGF-beta-induced increase in FMG contraction by keloid fibroblasts, but not normal fibroblasts, was mediated by the autocrine production of PDGF. Therefore, fibroblasts isolated from different scars exhibit varied degrees of FMG contraction. In addition, the mechanism underlying growth factor-mediated contraction differed vastly among fibroblasts of different scar origin. The significance of these differences in growth factor-mediated FMG contraction is discussed.

In vitro fibroplasia: matrix contraction, cell growth, and collagen production of fibroblasts cultured in fibrin gels.

Extracellular matrix (ECM) reorganization, cell growth, and collagen synthesis/deposition are key features of fibroplasia during tissue repair. An in vitro fibrin gel culture model system simulating fibroplasia of wound repair was characterized. In the model system, fibrin gels were stabilized on plastic culture plates as hemispheres. In this way, fibroblasts were able to reorganize fibrin fibrils, resulting in a measurable decrease in gel thickness with no change in gel diameter, thereby producing a matrix with tension relevant to that of a repairing tissue. Within the study period, human dermal fibroblasts exhibited dynamic activities in cell growth and in reorganization and remodeling of the fibrin matrix. In the first 2 days of culture, fibroblasts quickly reorganized the fibrin matrix to 10% of its original thickness. Fibroblast proliferation occurred at a much slower rate compared to monolayer cultures. Proliferation continued at the same rate throughout the study in contrast to monolayer cultures, which ceased proliferation at confluence. Collagen synthesis was detected as early as the second day in culture. Type I collagen was the major collagen synthesized by fibroblasts with small amounts of type V and type III collagen. Collagen from either monolayer or fibrin gel cultures appeared identical when analyzed by two-dimensional peptide mapping of their CNBr fragments. Although collagen was detected biochemically from Day 2, organized collagen fibrils were apparently only in the later stage of cultures in transmission electron micrographs. Also, at this time, fibrin fibrils were largely removed and the matrix was filled with collagen fibrils and other filamentous ECM. The growth factor TGF-beta stimulated both fibrin gel contraction and collagen synthesis by fibroblasts. Therefore, using the model system, we have demonstrated that fibroblasts can actively reorganize the fibrin matrix and subsequently remodel it into a collagen-containing scar-like tissue. The unique features of this model system allow for creative designs in studying the complex mechanisms underlying tissue repair.

Use of sodium ipodate in management of hyperthyroidism in subacute thyroiditis.

Five hyperthyroid patients (two men and three women) with typical features of subacute thyroiditis were treated with sodium ipodate (Oragrafin; 0.5 g, orally daily or every other day) for 15-60 days; the treatment was stopped when both serum T4 and T3 levels were normal. All patients studied demonstrated a prompt normalization of serum T3, improvement in clinical symptoms of hyperthyroidism, and/or weight gain. We observed no side-effects of treatment with sodium ipodate. Our data suggest that sodium ipodate is a safe and effective agent for management of hyperthyroidism in subacute thyroiditis.

Modulation of collagen synthesis by transforming growth factor-beta in keloid and hypertrophic scar fibroblasts.

Keloid and hypertrophic scars are fibrous growths characterized by overabundant collagen deposition. We examined the effect of transforming growth factor-beta (TGF-beta), a known stimulant for the production of connective tissue matrices, on the rate of collagen synthesis in keloid fibroblasts (KFs), hypertrophic scar fibroblasts (HSFs), and normal skin fibroblasts (NSFs). Fibroblasts were cultured in three-dimensional fibrin-gel matrices in the presence or absence of TGF-beta (5 ng/ml) or anti-TGF-beta neutralizing antibody (50 micrograms/ml). Secreted collagen levels, labeled with 3H-proline, were measured after 48 hours. KFs produced up to 12 times more collagen than NSFs, and up to 4 times more than HSFs. Although KFs increased their rate of collagen production by up to 2.7 times in response to TGF-beta, HSFs and NSFs did not (p = 0.065). Anti-TGF-beta antibody reduced the rate of collagen synthesis of KFs by 40% (p = 0.003), although it did not suppress collagen production in HSFs (p = 0.06) and NSFs (p = 0.75). We conclude that although KFs and HSFs are similar in that they both overproduce collagen, they are different in that only KFs display a marked sensitivity to TGF-beta, which is abundant during the proliferative phase of wound healing.

Hemagglutinins and bacterial agglutinins of earthworms.

The biological roles of invertebrate agglutinins have been and remain an unresolved subject of controversy. Classical studies on agglutinins, beginning with the pioneer work of Noguchi (1903) on Limulus polyphemus and Homarus americanus have emphasized their hemagglutinating properties, an approach that has been criticized for its lack of biological relevance. While erythrocyte agglutination has proven useful for determining various properties of invertebrate agglutinins, it does not address the question of their natural function. More recently, invertebrate agglutinins have been investigated for their ability to interact with pathogenic agents such as bacteria (for review, see Pistole, 1982), yeast (Van der Knapp et al., 1982; Renwrantz and Stahmer, 1983) and parasitic protozoans (Ingram et al., 1984). In addition, the possible relationship of agglutinins to defense mechanisms of both vertebrates and invertebrates has been indicated by the observation that limulin, the major agglutinin of Limulus polyphemus, bears a number of similarities to vertebrate C-reactive proteins (Robey and Liu, 1981). In annelids, there have been no studies on bacterial agglutinins prior to our work with Lumbricus (Stein et al., 1985; Stein et al., submitted). Earthworms are particularly appropriate for studying bacterial agglutinins since their coelomic fluid contains constant low levels of bacteria and fungal spores, and their agglutinins are both naturally occurring and inducible. Although our initial studies on Lumbricus agglutinins were directed toward their hemagglutinating properties, our recent observations using bacteria have allowed us to reach the following conclusions: 1) Lumbricus coelomic fluid normally contains agglutinins against both erythrocytes and bacteria. After injecting worms with either erythrocytes or bacteria, agglutinin titers increase in coelomic fluid. This increase appears to be due to both an increase in numbers of agglutinins as well as levels of specific agglutinins. 2) Absorption studies, temperature effects and sugar inhibition analyses suggest that agglutinins which bind to erythrocytes are identical to bacterial agglutinins, but there are additional agglutinins capable of reacting only with bacteria. 3) The inducibility and bacterial binding properties of Lumbricus agglutinins suggest that they serve an immune function by participating in the earthworm's defense against bacterial infection. In this sense, the agglutinins serve as a humoral surveillance system that entraps and prevents the multiplication of pathogenic bacteria.