Role of elevated plasma transforming growth factor-beta1 levels in wound healing. (1/98)

Transforming growth factor (TGF)-beta1 plays a central role in wound healing. Wounds treated with neutralizing antibody to TGF-beta1 have a lower inflammatory response, reduced early extracellular matrix deposition, and reduced later cutaneous scarring, indicating the importance of local tissue TGF-beta1. By contrast, increasing the local, tissue levels of TGF-beta1 increases the early extracellular matrix deposition but does not alter scar formation. Increased levels of plasma TGF-beta1 correlate with increased fibrogenesis in the lung, kidneys, and liver. The aim of the present study was to investigate the role of elevated systemic levels of TGF-beta1 on wound healing. We used transgenic mice that express high levels of active TGF-beta1 and have elevated plasma levels of TGF-beta1 and wild-type mice of the same strain as controls. Incisional wounds and subcutaneously implanted polyvinyl alcohol (PVA) sponges were analyzed. Surprisingly, cutaneous wounds in transgenic, TGF-beta1-overexpressing mice healed with reduced scarring accompanied by an increase in the immunostaining for TGF-beta3 and TGF-beta-receptor RII and a decrease in immunostaining for TGF-beta1 compared with wounds in control mice. By contrast, the PVA sponges showed the opposite response, with PVA sponges from transgenic mice demonstrating an enhanced rate of cellular influx and matrix deposition into the sponges accompanied by an increase in the immunostaining for all three TGF-beta isoforms and their receptors compared with PVA sponges from control mice. Together, the data demonstrate that increased circulating levels of TGF-beta1 do not always result in increased expression or activity in selected target tissues such as the skin. The two wound models, subcutaneously implanted PVA sponges and cutaneous incisional wounds, differ significantly in terms of host response patterns. Finally, the data reinforce our previous observations that the relative ratios of the three TGF-beta isoforms is critical for control of scarring.  (+info)

A novel immunological model for the study of prostate cancer. (2/98)

The Dunning R-3327 rat prostatic adenocarcinoma is a widely accepted model for in vivo experimental studies of prostate cancer. We have previously derived phenotypically distinct cell lines from a s.c. tumor resulting from the inoculation of the R-3327-5 subclone into Copenhagen rats. In this study, we report studies using a gelatin sponge model for the delivery of tumor cells and the retrieval of tumor-specific leukocytes responsive to different prostatic cell lines. S.c. preimplanted sponges were inoculated with tumor cells previously selected for differential properties of tumor formation and metastasis and examined for leukocyte content at time points of 1, 3, and 5 weeks after tumor cell inoculation. Cytospin and flow cytometric analyses revealed fewer tumor-associated leukocytes present in sponges inoculated with tumorigenic R-3327-5' and R-3327-5'B lines, with lesser sponge degradation, than in experiments with the nontumorigenic R-3327-5'A line, suggestive of a tumor cell-induced immunomodulatory mechanism. Morphological studies indicate an intermittent tumor growth pattern that gradually disappears in sponges inoculated with the nontumorigenic R-3327-5'A cells but a robust growth pattern in sponges inoculated with the tumorigenic cell lines. Cytokine analyses show the secretion of higher levels of active transforming growth factor-beta by the more invasive and metastatic lines. Total transforming growth factor-beta levels are higher in the epithelial, tumorigenic R-3327-5'B line. Additionally, the more tumorigenic lines secrete interleukin 10, a potent immunosuppressive molecule. In this report, we demonstrate the ability to retrieve viable leukocyte populations from a prostate tumor line bearing sponges, which offers an important model for further in vitro and in vivo manipulations and holds promise for testing adoptive immunotherapeutic strategies.  (+info)

Treatment of infective and potentially infective complications of vascular bypass grafting using gentamicin with collagen sponge. (3/98)

The use of gentamicin with collagen sponge (GCS) in treating patients with infective and potentially infective complications of vascular bypass grafting was reviewed. GCS was used in 25 patients. These were: 11 in situ applications to a proven graft infection, 2 to a superficial wound infection over an underlying graft, 4 at removal of an infected prosthesis, 4 for a persistent lymphatic leak, 3 for an anastomotic aneurysm and one for an anastomotic dehiscence. The GCS was used with rifampicin-soaked collagen impregnated Dacron in 3 of these patients. Of the 11 in situ treatments of a graft infection with GCS, 7 infections were successfully aborted, 3 grafts were removed resulting in 2 patients losing a leg and one patient died before the outcome was known. None of the other patients treated with GCS subsequently had infective sequelae. GCS is a simple, safe and often effective treatment when dealing with these difficult complications of arterial surgery, the use of which requires greater recognition.  (+info)

Sponge delivery variables and tissue levels of 5-fluorouracil. (4/98)

AIM: To study how the delivery of 5-fluorouracil (5-FU) to ocular tissues is affected by altering delivery variables. METHOD: Sponge(s) soaked in radiolabelled 5-FU were placed between the conjunctiva and sclera of pig eyes. Application time, sponge size, sponge make (Altomed, Weck, Merocel), and 5-FU concentration were varied. Conjunctival and scleral tissue levels were determined in samples taken from the application site. RESULTS: Dose-response curves for scleral and conjunctival 5-FU levels against application time showed increasing tissue levels that reached a plateau after 2-3 minutes. Application beyond 3 minutes did not increase tissue levels. There was no difference in tissue levels between 7x4 and 3. 5x2 mm sponges. Altomed sponges produced 5-FU tissue levels that were twice as high as those obtained with Weck-cell (p<0.01) or Merocel (p<0.02) sponges. Changing the 5-FU concentration from 25 mg/ml to 6.25 mg/ml reduced the conjunctival concentration by a factor of 3.5 (p<0.003). CONCLUSION: Application time up to 3 minutes, sponge make, and 5-FU concentration can have a large effect on the tissue delivery of 5-FU. Application time beyond 3 minutes, using 3.5x2 mm or 7x4 mm sponges, and replacing sponges every minute did not have a significant effect on tissue levels. This study models the effect that different variables can have on the ocular tissue levels of an antimetabolite applied intraoperatively.  (+info)

Optimization of the weck-Cel collection method for quantitation of cytokines in mucosal secretions. (5/98)

Measurement of immune components in mucosal secretions is important for the evaluation of local immunity at the mucosal surfaces. The Weck-Cel ophthalmic sponge provides a method for the collection of these secretions. The sponge absorbs a relatively large volume of material, therefore allowing for quantitation of multiple immune components. Additionally, it provides a method in which the same device may be used to collect specimens from different mucosal sites, such as the genital tract and oral cavity. This sampling technique has successfully been applied for collection and measurement of antibody in oral and genital tract secretions. The purpose of this work was to optimize the extraction of protein from the sponge matrix. Of particular interest was the recovery of cytokines from the sponge. Satisfactory recovery of the cytokines interleukin 1beta (IL-1beta), IL-2, IL-5, IL-12, IL-6, IL-8, IL-10, and granulocyte-macrophage colony-stimulating factor was obtained. However, IL-4 and gamma interferon recovery rates remained low. Using an alteration of the published extraction method, cytokine concentrations were measured in cervical secretions from women using oral contraceptives. The data revealed detectable concentrations of IL-6, IL-10, IL-8, and IL-12 on cycle days 9 and 20. The proposed technique provides an easy, practical, and consistent method for collection of nonconventional body fluids, such as cervicovaginal fluids and saliva, for the assay of immunoglobulins and several cytokines.  (+info)

Imaging features of gossypiboma: report of two cases. (6/98)

Recognition of postoperatively retained foreign body referred euphemistically as gossypiboma is essential but is very often considerably delayed. Legal implications as well as confusing configuration patterns cause considerable dilemma in the accurate diagnosis. We present computed tomographic features of gossypiboma in two patients who presented with symptoms of fever and pain in the immediate post-operative period. A prospective radiological diagnosis is essential for further management in these patients.  (+info)

Effect of IOP elevation on matrix metalloproteinase-2 in rabbit anterior chamber. (7/98)

To investigate changes in the level of matrix metalloproteinase-2 (MMP-2) in the anterior chamber of rabbit with intraocular pressure (IOP) elevation. The IOP was elevated with scleral encircling in 12 rabbits. In the control group (4 rabbits), IOP was not changed after scleral encircling, and in group 1 (4 rabbits) and 2 (4 rabbits), IOP was elevated about 10 and 20 mmHg respectively after scleral encircling. At 2 days after scleral encircling, aqueous sampling was performed and levels of MMP-2 were checked by Western blots and gelatin zymograms. The greater the IOP elevation, the more MMP-2 expression in the anterior chamber by Western blots and gelatin zymograms. The increase in MMP-2 expression in response to IOP elevation may have important implications for the IOP feedback control mechanism.  (+info)

Antiangiogenic effect of KR31372 in rat sponge implant model. (8/98)

A rat sponge implant model was used to examine the antiangiogenic effect of KR31372. Topical administration of angiotensin II (AII, 100 ng, daily) into the sponges enhanced the basal sponge-induced neovascularization, leading to higher clearance of (99m)Tc, increased retention of dye in the vessels, and increased numbers of blood vessels. These AII-induced changes were significantly suppressed by oral administration of KR31372 (1 mg/kg for 7 days). Angiogenic effect of recombinant human VEGF(165) (200 ng) was modestly higher than that of AII, which was also significantly inhibited by KR31372. KR31372-mediated suppression of (99m)Tc clearance was reversed by glibenclamide. Levcromakalim showed a modestly suppressive effect on the AII-induced angiogenesis. In conclusion, KR31372 exerted a strong inhibitory effect on the sponge-induced neovascularization, in part, through mediation of glibenclamide-sensitive K(+) channel activation. It is suggested that it may have therapeutic potential in the treatment of angiogenic disorders.  (+info)

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