Acne Scars

J Speech Lang Hear Res. 2009 Aug; 52(4): 1008-20Welham NV, Montequin DW, Tateya I, Tateya T, Choi SH, Bless DMPURPOSE: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. METHOD: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic fibroblast growth factor (bFGF), chronic vocal fold scar treated with saline (sham treatment), and unscarred untreated control. Following tissue harvest, histological and immunohistochemical data were collected to confirm extracellular matrix alteration in the chronic scar group; acoustic, aerodynamic, and high-speed digital imaging data were collected using an excised larynx setup in all groups. Phonation threshold pressure (P(th)), glottal resistance (R(g)), glottal efficiency (E(g)), vibratory amplitude, and vibratory area were used as dependent variables. RESULTS: Chronically scarred vocal folds were characterized by elevated collagen Types I and III and reduced hyaluronic acid abundance. Phonation was achieved, and data were collected from all control and bFGF-treated larynges; however, phonation was not achieved with 3 of 6 chronically scarred and 1 of 6 saline-treated larynges. Compared with control, the chronic scar group was characterized by elevated P(th), reduced E(g), and intralarynx vibratory amplitude and area asymmetry. The bFGF group was characterized by P(th) below control-group levels, E(g) comparable with control, and vocal fold vibratory amplitude and area symmetry comparable with control. The sham group was characterized by P(th) comparable with control, E(g) superior to control, and vocal fold vibratory amplitude and area symmetry comparable with control. CONCLUSIONS: The excised larynx model reported here demonstrated robust deterioration across phonatory indices under the scar condition and sensitivity to treatment-induced change under the bFGF condition. The improvement observed under the sham condition may reflect unanticipated therapeutic benefit or artifact. This model holds promise as a tool for the functional characterization of biomechanical tissue changes resulting from vocal fold scar and the evaluation of experimental therapies.

Lasers Surg Med. 2009 Jul 28; Holden PK, Li C, Da Costa V, Sun CH, Bryant SV, Gardiner DM, Wong BJOBJECTIVES: Laser reshaping of cartilage is an emerging technology aimed at replacing conventional techniques for aesthetic and reconstructive surgery. Little is known about the mechanisms of wound healing following the photothermal heating during laser reshaping and, ultimately, how collagen remodels in the irradiated tissue. Healthy hyaline and elastic cartilage as found in the ear, nose, larynx, and trachea does not express collagen type I which is characteristic of fibro-cartilage and scar tissue. The aim of the study was to determine if collagen I and II gene expression occurs within laser irradiated rabbit septal cartilage. METHODS: Nasal septum harvested from freshly euthanized New Zealand White rabbits were irradiated with an Nd:YAG laser. After 2 weeks in culture, the laser spot and surrounding non-irradiated regions were imaged using immunofluorescence staining and evaluated using reverse transcription polymerase chain reaction (RT-PCR) to determine the presence of collagen I and II, and ascertain collagen I and II gene expression, respectively. RESULTS: All laser irradiated specimens showed a cessation in collagen II gene expression within the center of the laser spot. Collagen II was expressed in the surrounding region encircling the laser spot and within the non-irradiated periphery in all specimens. Immunohistochemistry identified only type II collagen. Neither collagen I gene expression nor immunoreactivity were identified in any specimens regardless or irradiation parameters. CONCLUSIONS: Laser irradiation of rabbit septal cartilage using dosimetry parameters similar to those used in laser reshaping does not result in the detection of either collagen I gene expression or immunoreactivity. Only collagen type II was noted after laser exposure in vitro following cell culture, which suggests that the cellular response to laser irradiation is distinct from that observed in conventional wound healing. Laser irradiation of cartilage can leave an intact collagen matrix which likely allows chondrocyte recovery on an intact scaffold. Lasers Surg. Med. (c) 2009 Wiley-Liss, Inc.

Handchir Mikrochir Plast Chir. 2009 Jul 28; Hold A, Kamolz L, Frey MBACKGROUND: Due to the improvement of surgery and intensive care more and more patients survive even severe burn injuries. Therefore we have to pay attention not only to survival alone but also to the achievement of a good quality of life. Thereby, one of the most important aspects is sufficient tissue coverage. After appropriate debridement functionally important structures may be exposed. Therefore, these areas require more than split skin coverage. These cases necessitate flap coverage for preservation of function or, respectively, limb salvage. In secondary reconstruction flaps are commonly used for scar revision. The aim of this study is to give more detailed information about the need for flaps in burn surgery. PATIENTS AND METHODS: All burn patients of our burn centre who received free or local flap coverage between January 1997 and February 2008 were analysed retrospectively. We evaluated the following parameters: indication (acute or late), flap type (pedicled or free flap), localisation, cause of accident and complication rate. Small local flaps like Z-plasties have been excluded. RESULTS: 45 patients have been included into this study. They received 53 flaps. In 53% the cause of accident was flame, in 22% scald and in 24% electrical burn, whereby electrical burn injuries most frequently required flap coverage related to their incidence. Most of the flaps have been performed for primary reconstruction. More than half of all flaps have been used for the upper extremity, concerning just the hand in 36%, 19% for the lower extremity, 15% for the trunk and 11% for the head. There have been three total flap failures during the study period. In all other cases we reached good results. Two of these flap failures occurred during the vulnerable phase between the 6th and the 21st day after trauma. CONCLUSION: Limb salvage was the dominant indication for primary reconstruction compared to the improvement of function and aesthetics for secondary reconstruction. The timing of reconstruction has an important influence on the flap outcome and has to be considered when the decision for reconstruction is made. So, if possible, the period between the 6th and the 21st day should not be chosen for flap coverage.

J Burn Care Res. 2009 Jun 5; Harte D, Gordon J, Shaw M, Stinson M, Porter-Armstrong AThis pilot study investigates whether pressure and silicone therapy used simultaneously are more effective in treating multiple characteristics of hypertrophic scars than pressure alone. A pilot randomized controlled trial was conducted. Twenty-two participants with hypertrophic burn scars were randomized to receive Jobskin pressure garments and Mepiform silicone sheeting or Jobskin pressure garments alone. The Vancouver Scar Scale (VSS) was used to measure multiple scar characteristics at baseline, week 12, and week 24. No statistically significant difference was found in the rate of change of the VSS scores between the pressure therapy (PT) group and the pressure therapy and silicone group at week 12 or week 24; however, the mean scores of both groups reduced over 24 weeks. There were no statistically significant changes in the VSS subscores (scar height, vascularity, pliability, and pigmentation) from baseline to week 12 or week 24. A statistically significant relationship was observed between the VSS score and TBSA burned (

Arch Dermatol Res. 2009 Jul 28; Gragnani A, Warde M, Furtado F, Ferreira LMAs acute burn patients have experienced increasing survival rates, the number of patients who need specific care due to aberrant scarring is also increasing. The burned skin often responds with fibrotic tissue proliferation, which can lead to a hypertrophic scar or a keloid. Non-physiologic scars are mostly not acceptable for the burn patient. Intradermal and topical therapy in burns comprise the treatment of the skin injury and its possible texture, elasticity and color alterations with the aid of active substances that result in fibroblastic modulation. An alteration of cytokine levels may mediate these effects, and evidences suggest that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF)-beta(1). The addition of tamoxifen, a non-steroidal anti-estrogen, usually used in breast cancer, to standard treatment may lead to improved wound healing in keloids by decreasing the expression of TGF-beta(1), with the consequent inhibitions of both fibroblast proliferation and collagen production. Topical tamoxifen citrate chemical treatment has been shown to improve scarring. However, prospective studies must be undertaken to validate the inclusion of tamoxifen into standard clinical practice.

Orthopedics. 2009 Jun; 32(6): Crawford EA, King JJ, Fox EJ, Ogilvie CMPosttraumatic fat necrosis and lipoatrophy can occur in the subcutaneous fat following falls, blunt injury, surgery, and minor procedures or injections. While these processes have no inherent serious medical consequences, they occasionally require treatment due to severe or concerning symptoms. Three patients (all women; average age, 47 years) who sustained blunt trauma to the pelvis and were diagnosed with posttraumatic fat necrosis or lipoatrophy were retrospectively identified from our orthopedic oncology records. All patients recalled blunt trauma to the posterior pelvis just prior to symptom onset; 2 patients fell down stairs and 1 fell from a bed. Chief symptoms were a painful mass, a painless mass, and chronic pain in the injured area. Magnetic resonance imaging (MRI) revealed atrophy of the subcutaneous fat in all cases and a small mass in 1 patient. A bright linear signal was seen on T2-weighted, fat-saturated images in 2 cases, likely representing scar tissue. One patient with chronic pain underwent surgery to provide better soft tissue coverage in the area of atrophic fat. The other 2 patients did not undergo surgical treatment: 1 was treated at a pain center for reflex sympathetic dystropy-type pain, and 1 remained pain free. Blunt trauma with subsequent fat atrophy and necrosis manifests as a mass, a subcutaneous fat defect, and even as chronic pain. Characteristic MRI findings are often sufficient for diagnosis, but any indeterminate masses should be further evaluated to rule out aggressive or malignant neoplasms. Chronic unrelenting pain despite treatment may be related to posttraumatic reflex sympathetic dystropy-like symptoms.

J Pediatr Surg. 2009 Aug; 44(8): 1529-33Raval MV, Browne M, Chin AC, Zimmerman D, Angelos P, Reynolds MPURPOSE: Total thyroidectomy (TT) is a safe and efficacious treatment of malignant thyroid disease in children. The role of TT in benign thyroid disease is less well-defined. The goal of this study was to compare the safety of TT performed for benign and malignant disease. METHODS: The medical records of 31 patients undergoing TT from January 2000 to June 2007 at a single center were reviewed. The benign cohort totaled 15 patients consisting of 12 with Graves' disease, 2 with hyperthyroidism, and 1 with large and symptomatic multinodular goiter. The malignant cohort totaled 16 patients consisting of 9 with malignant disease, 4 with a nodule and history of cancer or radiation exposure, and 3 with RET proto-oncogene mutations. RESULTS: The most common complication was transient hypocalcemia observed in 7 (46%) of 15 patients with benign disease and 9 (56%) of 16 patients with malignancy (P = .72). Permanent hypocalcemia, defined as need for calcium supplement 6 months postprocedure, was observed in 1 patient with benign disease (6.67%) and 1 patient with malignancy (6.25%; P = 1.0). A single parathyroid gland was reimplanted in 2 patients with malignancy and 2 patients with benign disease (P = 1.0). One case of keloid scar was noted, and no cases of recurrent laryngeal nerve palsy, nerve paralysis, tracheal injury, tracheostomy, or wound infection were encountered in either cohort. There were no cases of relapse hyperthyroidism in the benign cohort. CONCLUSIONS: Similar rates of postoperative complications can be expected with TT for benign thyroid disease as compared to TT for malignant disease. Total thyroidectomy is a safe treatment option for benign thyroid disease in children.

Burns. 2009 Jul 2; Grishkevich VMThe new method for postburn neck contracture management is presented. The method is found to be most effective when using the local flap procedures on patients who cannot undergo complex and long surgical procedures that are aimed at both contracture elimination and neck skin restoration (children, elderly patients, patients with inadequate donor sites, and patients with cosmetically acceptable scar appearance). The method consists of the opposite transposition of trapezoid scar-fascial flaps which are prepared one on each antero-lateral neck surface. Both flaps include scars, fat, platysma and deep cervical fascia. As a result of the trapeze-flap plasty, the anterior surface of the neck is lengthened approximately by 100-200%, the contracture is eliminated and mentocervical angle and head movement are restored. The flaps have reliable blood circulation through the superficial cervical artery perforators, therefore flap loss is rare. The functional results were good in 24 out of 26 patients. The flaps surface does not decrease; therefore, the mild contracture becomes an exception.

Ann Plast Surg. 2009 Jun 16; Tindholdt TT, Tønseth KAThe aim of this study was to examine pressure sensitivity at the donor site after breast reconstruction with deep inferior epigastric artery perforator (DIEAP). In a cross-sectional survey, 2 groups of patients were analyzed. The DIEAP group consisted of 30 women who had previously had secondary breast reconstruction with DIEAP flap after mastectomy for breast cancer. The control group consisted of 7 women with no previous abdominal incisions planned for secondary breast reconstruction with DIEAP. Pressure thresholds were tested within the margins of the abdominal wall using Semmes-Weinstein monofilaments. In the DIEAP group a pattern of higher pressure thresholds was observed in the proximity of the scar. Comparing the 2 groups, significant higher pressure thresholds were found in the DIEAP group in the scar on both sides and in the midline from the scar to the umbilical level. Our data show that the abdominoplasty performed during breast reconstruction with DIEAP reduces cutaneous sensitivity in the donor site area.

Development. 2009 Aug; 136(16): 2849-60Liu R, Abreu-Blanco MT, Barry KC, Linardopoulou EV, Osborn GE, Parkhurst SMWiskott-Aldrich Syndrome (WAS) family proteins are Arp2/3 activators that mediate the branched-actin network formation required for cytoskeletal remodeling, intracellular transport and cell locomotion. Wasp and Scar/WAVE, the two founding members of the family, are regulated by the GTPases Cdc42 and Rac, respectively. By contrast, linear actin nucleators, such as Spire and formins, are regulated by the GTPase Rho. We recently identified a third WAS family member, called Wash, with Arp2/3-mediated actin nucleation activity. We show that Drosophila Wash interacts genetically with Arp2/3, and also functions downstream of Rho1 with Spire and the formin Cappuccino to control actin and microtubule dynamics during Drosophila oogenesis. Wash bundles and crosslinks F-actin and microtubules, is regulated by Rho1, Spire and Arp2/3, and is essential for actin cytoskeleton organization in the egg chamber. Our results establish Wash and Rho as regulators of both linear- and branched-actin networks, and suggest an Arp2/3-mediated mechanism for how cells might coordinately regulate these structures.

Appl Microbiol Biotechnol. 2009 Jul 25; McCleary WRThe ability to control the expression of chromosomal genes is important for many applications, including metabolic engineering and the functional analysis of cellular processes. This mini-review presents recent work on the application of techniques that allow researchers to replace a chromosomal promoter with one designed for a specific level of activity, thereby exerting precise transcriptional control while retaining the natural genetic context of a gene or operon. This technique, termed promoter swapping, involves the creation of a PCR product that encodes a removable antibiotic resistance cassette and an engineered promoter. Short homology sequences on the ends of the PCR fragment target it for homologous recombination with the chromosome catalyzed by phage-derived recombination proteins. After the PCR product is introduced by electroporation into an appropriate acceptor strain, antibiotic resistance selects the desired recombination products. The antibiotic resistance cassette is then removed from the strain by site-specific recombination leaving the engineered promoter precisely positioned upstream of a target gene but downstream of a short scar consisting of a single site-specific recombination site.

Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in inflammation, wound healing and other pathological processes after neurological disorders. MMP-2 promotes functional recovery after spinal cord injury (SCI) by regulating the formation of a glial scar. In the present study, we aimed to investigate the expression and/or activity of several MMPs, after SCI and human umbilical cord blood mesenchymal stem cells (hUCB) treatment in rats with a special emphasis on MMP-2.

Treatment with hUCB after SCI altered the expression of several MMPs in rats. MMP-2 is upregulated after hUCB treatment in spinal cord injured rats and in spinal neurons injured either with staurosporine or hydrogen peroxide. Further, hUCB induced upregulation of MMP-2 reduced formation of the glial scar at the site of injury along with reduced immunoreactivity to chondroitin sulfate proteoglycans. Blockade of MMP-2 activity in hUCB cocultured injured spinal neurons reduced the protection offered by hUCB indicated the involvement of MMP-2 in the neuroprotection offered by hUCB.

Based on these results, we conclude that hUCB treatment after SCI upregulate MMP-2 levels and reduce the formation of the glial scar thereby creating an environment suitable for endogenous repair mechanisms.


"Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury."
Neurobiol Dis. 2009 Jul 22; Veeravalli KK, Dasari VR, Tsung AJ, Dinh DH, Gujrati M, Fassett D, Rao JS

J Mol Cell Cardiol. 2009 Jul 22; Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NGThe dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also directly modulate the inflammatory and reparative response. During the inflammatory phase of healing, rapid activation of matrix metalloproteinases (MMP) causes degradation of the cardiac extracellular matrix. Matrix fragments exert potent pro-inflammatory actions, while MMPs process cytokines and chemokines altering their biological activity. In addition, vascular hyperpermeability results in extravasation of fibronectin and fibrinogen leading to formation of a plasma-derived provisional matrix that serves as a scaffold for leukocyte infiltration. Clearance of the infarct from dead cells and matrix debris is essential for resolution of inflammation and marks the transition to the proliferative phase. The fibrin-based provisional matrix is lysed and cellular fibronectin is secreted. ED-A fibronectin, mechanical tension and Transforming Growth Factor (TGF)-beta are essential for modulation of fibroblasts into myofibroblasts, the main collagen-secreting cells in the wound. The matricellular proteins thrombospondin-1 and -2, osteopontin, tenascin-C, periostin, and secreted protein acidic and rich in cysteine (SPARC) are induced in the infarct regulating cellular interactions and promoting matrix organization. As the infarct matures, matrix cross-linking results in formation of a dense collagen-based scar. At this stage, shielding of fibroblasts from external mechanical tension by the mature matrix network may promote deactivation and cellular quiescence. The components of the extracellular matrix do not passively follow the pathologic alterations of the infarcted heart but critically modulate inflammatory and reparative pathways by transducing signals that affect cell survival, phenotype and gene expression.

Am J Dermatopathol. 2009 Jul 23; Wiedemeyer K, Kutzner H, Abraham JL, Thakral C, Carlson JA, Tran TA, Hausser I, Hartschuh WGadolinium (Gd) is associated with nephrogenic systemic fibrosis (NSF), a severe disorder mimicking scleroderma with involvement of the skin, lungs, heart, liver, and muscles. There is strong evidence that specific Gd-containing contrast agents (GCCAs) used in magnetic resonance imaging can cause NSF when administered to patients with chronic kidney disease. We present the 8-year history of cutaneous NSF with osseous metaplasia that occurred in a 56-year-old man with dialysis-dependent renal failure who was exposed to GCCA [gadopentate dimeglumine (Magnevist; Bayer Schering Pharma AG, Pittsburgh, PA)]. Three months after exposure to GCCA, he developed pruritic, pigmented patches that slowly coalesced and darkened over 8 years. Although not recognized at onset, skin biopsy showed typical histology of NSF affecting the entire dermis: CD34/procollagen I spindle cells associated with fibrosis. Biopsy performed 6 years later showed superficial scar-like fibrosis that was CD34/procollagen I and had numerous elastocollagenous balls (refractile elastic fibers surrounded by coarse collagen). Biopsy 7 years later showed the superimposition of osseous metaplasia on elastocollagenous balls. Both of these later biopsies had typical NSF histology affecting the deep dermis and subcutis. Over time, there was progressive diminishment of CD34 and procollagen I+ cells and an increase in FXIIIa+ and CD68 cells. Scanning electron microscopy and energy-dispersive x-ray spectroscopy showed Gd deposits in all areas of typical NSF histology but not in the regions of scar-like fibrosis, elastocollagenous balls, or osseous metaplasia. We suspect that the later changes may represent a late, involuting stage of NSF.

J Craniofac Surg. 2009 Jul; 20(4): 1280-2Hwang KThe aim of this study is to determine the safety and complication of subciliary approach through the retrospective review of our experiences. From 2005 through 2008, the subciliary skin-muscle flap methods were used in 30 patients undergoing medial orbital wall reconstruction. Preoperative and postoperative ophthalmic findings including diplopia, Hertel exophthalmometry, and occurrence of complications were checked. Resorbable polylactic acid sheet or porous polyethylene sheet was trimmed and molded in L shape, vertical portion to cover the medial wall defect and horizontal portion for stability in orbital floor.In the follow-up of diplopia, half of the patients (3 cases) presenting with diplopia improved during the first month of follow-up, and all of them improved by 6 month. For hypesthesia, all patients improved by 3 months. Enophthalmos of 1 patient improved after operation and did not recur. No patients complained of visible scar 6 months postoperatively, and no ectropion was observed.We think that medial orbital wall could be reconstructed safely through skin-muscle flap subciliary approach without resulting in ectropion or lacrimal canaliculus injury.

Ophthalmic Res. 2009 Jul 23; 42(3): 152-154Quijano C, Querques G, Massamba N, Soubrane G, Souied EHAim: To describe a patient with type 3 choroidal neovascularization (CNV) associated with fundus flavimaculatus (FFM), who underwent treatment with intravitreal ranibizumab. Methods: A 78-year-old woman diagnosed with FFM presented at our department complaining of decreased vision and metamorphopsia in her left eye. Upon a complete ophthalmologic examination, including best corrected visual acuity (BCVA), fundus autofluorescence, fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT), the patient was diagnosed with type 3 CNV associated with FFM, and was submitted to intravitreal ranibizumab injections at monthly intervals. Results: Six months after 3 monthly injections of ranibizumab, the patient's BCVA improved from 20/64 to 20/32. FA and ICGA revealed a type 3 CNV closure, and the SD-OCT scan showed a fibrous scar replacing the type 3 CNV, with resolution of serous retinal detachment. Conclusion: This case represents the first demonstration of type 3 CNV associated with FFM. Based on our findings, intravitreal ranibizumab may be considered as a therapeutic option for this rare association.

Br J Dermatol. 2009 Jul 14; Al-Refu K, Goodfield MSummary Background Scarring represents the single most debilitating aspect of discoid lupus erythematosus (DLE) in patients with cutaneous lesions alone. Despite this, there have been no studies which have attempted to classify the types of scars seen in this chronic disease. Objectives The aim was to classify the types of scars based on morphological description. Patients and methods Forty-five patients with histologically confirmed DLE were included in the study. In the assessment of the types of scars, the scars were scored initially according to their anatomical localization. Each anatomical area was assessed for the types of scars which occurred in these areas. Results Scars in patients with DLE were initially classified morphologically into six types according to the site of the scar and then each type was classified into subtypes according to the morphology of the scar. Scars were seen in the majority of the patients and scarring affected mostly areas including the scalp, other hairy areas such as the eyebrows, nonhairy areas, mucosa, fatty layers of the skin and the nails. This study demonstrated that scars may not only produce textural changes but may also produce pigmentary changes. It is possible that other types of scars may yet occur in DLE but have not so far been detected. Conclusions Early classification and identification of the types of scars in these patients may change management towards more aggressive therapy in those with continued disease activity, and it is possible that different types of scarring require different therapies.

J Oral Maxillofac Surg. 2009 Jul; 67(7): 1499-502Larrazabal-Morón C, Boronat-López A, Peñarrocha-Diago M, Peñarrocha-Diago MEpidermolysis bullosa (EB) represents a group of mainly hereditary skin disorders, manifested by an exceptional tendency of the skin and mucosa to form bullae and vesicles after minor friction and trauma. Oral features include repeated blistering, scar formation, elimination of buccal and vestibular sulci, and alveolar bone resorption. The use of endosseous implants in the fixed prosthetic rehabilitation of patients with recessive dystrophic EB might provide a considerably better outcome than conventional removable prosthetic methods. This clinical report describes the fixed rehabilitation with 2 implants placed simultaneously with bone graft in a partially edentulous patient diagnosed with recessive dystrophic EB. The implants, with simultaneous bone graft, were placed to decrease the number of surgical operations required, avoiding soft tissue ulcerations and discomfort in the patient. This treatment option appears to be favorable for recessive dystrophic EB patients compared with other options involving removable prostheses, which irritate the oral mucosa.

J Plast Reconstr Aesthet Surg. 2009 May 21; Ulrich D, Ulrich F, Unglaub F, Piatkowski A, Pallua NBACKGROUND: Hypertrophic scars and keloids are fibroproliferative skin disorders characterised by progressive deposition of collagen. Our study is designed to investigate the expression and concentration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in different types of scars and keloids. METHODS: Total RNA from 19 proliferative hypertrophic scar samples of patients with extended burns (total body surface area (TBSA): 21+/-12%), 18 mature hypertrophic scar samples from patients after elective surgery, 14 keloid samples and 18 normotrophic scar samples was, respectively, extracted, and then mRNA was isolated. Besides, biopsies were obtained from non-scarred skin of the patients and extraction of total RNA performed. Relative mRNA expression of MMP 2, MMP 9, TIMP 1 and TIMP 2 was measured with reverse transcriptase polymerase chain reaction (RT-PCR). Serum concentrations of MMP-1, -2, -9, TIMP-1, and -2 were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with extended hypertrophic scars after burn trauma presented a significantly higher TIMP-1 concentration (p

Clin Exp Dermatol. 2009 May 21; Pfistershammer K, Petzelbauer P, Stingl G, Mastan P, Chott A, Jäger U, Skrabs C, Geusau ASummary A patient with a 25-year history of rheumatoid arthritis and a 3-year history of methotrexate treatment developed a generalized papular rash. The papules rapidly became necrotic and then resolved, leaving a depressed scar. The rapid course of lesion development and regression was reminiscent of pityriasis lichenoides. Histology revealed a nodular infiltrate composed of a mixture of pleomorphic large B cells positive for CD20, CD30 and CD79a, and of small T cells positive for CD3 and CD4. The T cells had a striking angiocentric distribution, with some of the vessels exhibiting fibrinoid necrosis of the vessel wall reminiscent of lymphomatoid granulomatosis. However, B cells were consistently negative for Epstein-Barr virus (EBV) antigen expression. A thorough examination excluded involvement of organs other than the skin. Thus, this patient was classified as having a rare form of an EBV-negative primary cutaneous T-cell-rich B-cell lymphoma in association with methotrexate treatment.

Cell Transplant. 2009; 18(4): 477-86Fujimoto KL, Miki T, Liu LJ, Hashizume R, Strom SC, Wagner WR, Keller BB, Tobita KStem cells contained in the amniotic membrane may be useful for cellular repair of the damaged heart. Previously, we showed that amnion-derived cells (ADCs) express embryonic stem cell surface markers and pluripotent stem cell-specific transcription factor genes. These ADCs also possess the potential for mesoderm (cardiac) lineage differentiation. In the present study we investigated whether untreated naive ADC transplantation into the injured left ventricular (LV) myocardium is beneficial as a cell-based cardiac repair strategy in a rat model. ADCs were isolated from Lewis rat embryonic day 14 amniotic membranes. FACS analysis revealed that freshly isolated ADCs contained stage-specific embryonic antigen-1 (SSEA-1), Oct-4-positive cells, and mesenchymal stromal cells, while hematopoietic stem cell marker positive cells were absent. Reverse transcription-PCR revealed that naive ADCs expressed cardiac and vascular specific genes. We injected freshly isolated ADCs (2 x 10(6) cells suspended in PBS, ADC group) into acutely infarcted LV myocardium produced by proximal left coronary ligation. PBS was injected in postinfarction controls (PBS group). Cardiac function was assessed at 2 and 6 weeks after injection. ADC treatment attenuated LV dilatation and sustained LV contractile function at 2 and 6 weeks in comparison to PBS controls (p < 0.05, ANOVA). LV peak systolic pressure and maximum dP/dt of ADC-treated heart were higher and LV end-diastolic pressure and negative dP/dt were lower than in PBS controls (p < 0.05). Histological assessment revealed that infarcted myocardium of the ADC-treated group had less fibrosis, thicker ventricular walls, and increased capillary density (p < 0.05). The fate of injected ADCs was confirmed using ADCs derived from EGFP(+) transgenic rats. Immunohistochemistry at 6 weeks revealed that EGFP(+) cells colocalized with von Willebrand factor, alpha-smooth muscle actin, or cardiac troponin-I. Our results suggest that naive ADCs are a potential cell source for cellular cardiomyoplasty.

J Minim Invasive Gynecol. 2009 Jul-Aug; 16(4): 432-6Yang Q, Piao S, Wang G, Wang Y, Liu CSTUDY OBJECTIVE: To evaluate the effect of hysteroscopy in the treatment of caesarean section scar pregnancy. DESIGN: Retrospective review. PARTICIPANTS: Thirty-nine patients with cesarean scar pregnancy. INTERVENTIONS: Between January 2006 and June 2008, 39 patients with caesarean section scar pregnancy underwent hysteroscopic removal of conceptive tissues in our department. Their medical records were reviewed retrospectively. MEASUREMENTS AND MAIN RESULTS: The diagnosis was confirmed by serum human chorionic gonadotropic concentration and at ultrasonographic or magnetic resonance imaging. All patients underwent hysteroscopic removal of conceptive tissues under ultrasonographic guidance. Before surgery, 36 patients received 25mg of oral mifepristone, 25mg, twice a day for 3 days, and 3 patients received an injection of methotrexate salt, 50mg, and underwent preoperative bilateral uterine artery embolization. Results were reported as good in 37 patients; only 2 patients required additional surgery. CONCLUSION: Hysteroscopic removal of conceptive tissues implanted in a cesarean section scar seems to be a feasible and safe procedure that might be considered as a treatment option.

Oral Maxillofac Surg. 2009 Jul 21; Chrcanovic BR, Custódio AL, de Oliveira DRPURPOSE: The purpose of this study is to present an alternative method to the extraoral surgical approach to remove the elongated styloid process, the intraoral surgical approach, and discuss their advantages and disadvantages. A literature review is also presented. PATIENTS AND METHODS: A casuistic of intraoral surgical approach to remove the elongated styloid process is presented in five patients. RESULTS: Four patients experienced postoperative moderate pain and trismus for 1 week. Bilateral surgery in one patient caused severe trismus, great discomfort, and moderate difficulty in breathing. All were followed up for 6 months and showed complete relief of the oral pharyngeal symptoms and complete improvement in functional ability. DISCUSSION: The advantages of the external approach are good visualization and reduced possibility of deep neck space infection. The disadvantages are an external scar, longer duration of surgery, and risk of injury to the facial nerve. The advantages of the intraoral approach are that the method is safe, simple, and less time consuming and an external scar is avoided. The disadvantages are possible infection of deep neck spaces, risk of injury to major vessels, and poor visualization. CONCLUSIONS: Intraoral resection of the styloid process is a safe treatment technique of Eagle's syndrome. It is not recommended the bilateral intervention at the same surgery, because of possible great discomfort at postoperative time.

Prog Neurobiol. 2009 Feb 4; Wang W, Bu B, Xie M, Zhang M, Yu Z, Tao DThe cell cycle is a delicately manipulated process essential for the development, differentiation, proliferation and death of cells. Inappropriate activation of cell cycle regulators is implicated in the pathophysiology of a wide range of central nervous system (CNS) diseases, including both acute damage and chronic neurodegenerative disorders. Cell cycle activation induces the dividing astrocytes and microglia to activate and proliferate in association with glial scar formation and inflammatory factor production, which play crucial roles in the development of pathology in CNS diseases. On the other hand, in terminally differentiated neurons, aberrant re-entry into the cell cycle triggers neuronal death instead of proliferation, which may be a common pathway shared by some acquired and neurodegenerative disorders, even though multiple pathways of the cell cycle machinery are involved in distinct neuronal demise in specific pathological circumstances. In this paper, we first provide a concise description of the roles of cell cycle in neural development. We then focus on how neural cell cycle dysregulation is related to CNS diseases. Neuronal apoptosis is often detected in acute injury to the CNS such as stroke and trauma, which are usually related to the blockade of the cell cycle at the G1-S phase. In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Niemann-Pick disease type C, however, some populations of neurons complete DNA synthesis but the cell cycle is arrested at the G2/M transition. This review summarizes advances in findings implicating cell cycle machinery in neuronal death in CNS diseases.

Wound Repair Regen. 2009 Jul-Aug; 17(4): 559-68Song B, Zhang W, Guo S, Han Y, Zhang Y, Ma F, Zhang L, Lu KHypertrophic scarring remains a major problem for patients who have suffered from surgeries or burns. Vascularization plays an important role in the early phase of hypertrophic scarring. Therefore, the inhibition of angiogenesis might be used as a preventive strategy. In this study, we assessed the effect of anti-angiogenesis resulting from adenovirus-mediated METH1 (metalloprotease and thrombospondin1) gene expression on the hypertrophic scar formation in a rabbit ear model of hypertrophic scarring. We first investigated the number of microvessel and microcirculatory perfusion in untreated scars on days 10, 30, 60, and 90 after epithelialization. Then, we examined the effect of anti-angiogenesis by adenovirus-mediated METH1 expression on hypertrophic scar formation by calculating the scar elevation index, counting the microvessel and argyrophilic nucleolar organizer region particle, and detecting the amount of collagen on days 30 and 60 after treatment. We found that untreated scar tissues at the proliferative phase (days 10-60 after epithelialization) had a significantly higher density of microvessel and microcirculatory perfusion than those at the mature phase (day 90 after epithelization) (both p

J Plast Reconstr Aesthet Surg. 2009 Jul 17; Zhang GY, Cheng T, Zheng MH, Yi CG, Pan H, Li ZJ, Chen XL, Yu Q, Jiang LF, Zhou FY, Li XY, Yang JQ, Chu TG, Gao WYPeroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, and some studies have suggested a beneficial effect on organ fibrosis, but their effects on dermal cell growth and extracellular matrix (ECM) turnover are unknown. To investigate the effect of the PPAR-gamma agonist troglitazone on cell growth and matrix production in human dermal fibroblasts (HDF), HDF were cultured and grown in a different concentration of troglitazone. PPAR-gamma expression and matrix production were measured in HDF in the presence of troglitazone. The mRNA expressions of TGF-beta1, collagen I (Col I) and fibronectin (FN) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein of transforming growth factor-beta1 (TGF-beta1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of Col I and FN were determined by Western blotting. The mRNA expression of TGF-beta1, Col I and FN were significantly decreased in HDF in 15-30mumoll(-1) troglitazone compared to the control group with Dulbecco's modified Eagle's medium (P

Brain. 2009 Jul 16; Bacigaluppi M, Pluchino S, Jametti LP, Kilic E, Kilic U, Salani G, Brambilla E, West MJ, Comi G, Martino G, Hermann DMRecent evidence suggests that neural stem/precursor cells (NPCs) promote recovery in animal models with delayed neuronal death via a number of indirect bystander effects. A comprehensive knowledge of how transplanted NPCs exert their therapeutic effects is still lacking. Here, we investigated the effects of a delayed transplantation of adult syngenic NPCs-injected intravenously 72 h after transient middle cerebral artery occlusion-on neurological recovery, histopathology and gene expression. NPC-transplanted mice showed a significantly improved recovery from 18 days post-transplantation (dpt) onwards, which persisted throughout the study. A small percentage of injected NPCs accumulated in the brain, integrating mainly in the infarct boundary zone, where most of the NPCs remained undifferentiated up to 30 dpt. Histopathological analysis revealed a hitherto unreported very delayed neuroprotective effect of NPCs, becoming evident at 10 and 30 dpt. Tissue survival was associated with downregulation of markers of inflammation, glial scar formation and neuronal apoptotic death at both mRNA and protein levels. Our data highlight the relevance of very delayed degenerative processes in the stroke brain that are intimately associated with inflammatory and glial responses. These processes may efficaciously be antagonized by (stem) cell-based strategies at time-points far beyond established therapeutic windows for pharmacological neuroprotection.

J Cutan Pathol. 2009 Jul 10; Pongpudpunth M, Keady M, Mahalingam MBackground: The etiopathogenesis of dermatofibroma (DF), a common benign fibrohistiocytic tumor, is debatable. The goal of this study was to ascertain the density of elastic tissue fibers in DF in an effort to investigate whether this provides an insight into its etiopathogenesis. Method: Three groups comprising eight cellular DFs, eight paucicellular DFs and eight scars (control group) were stained with a modified Verhoeffs-van Gieson (without counterstain), and elastic fibers in three randomly selected fields within the lesional area/case semiquantitatively analyzed and examined in a blinded fashion. Result: The mean density of elastic tissue fibers in cellular DF was 6.81 (1.38-15.89); in paucicellular DF, 2.46 (0.14-5.79) and in scar, 2.95 (0.97-10.69). Overall, significant differences in density of elastic tissue fibers were observed only between cellular DF and the other two groups (vs. paucicellular variant, p = 0.03 and vs. scar, p = 0.05). Morphological changes observed included thickness, clumping, elongation and waviness (cellular DF) and margination of elastic tissue fibers (paucicellular variant). Conclusion: While the jury still appears to be out regarding the etiopathogenesis of DF, the reduction in density of elastic tissue fibers in the paucicellular variant compared with its cellular counterpart lends credence to the concept of evolutionary stages of DF. Pongpudpunth M, Keady M, Mahalingam M. Morphometric analyses of elastic tissue fibers in dermatofibroma: clues to etiopathogenesis?

J Cutan Pathol. 2009 Jul 15; Wang XQ, Phillips GE, Wilkie I, Greer R, Kimble RMBackground: Hypertrophic scars in burn victims usually occur after delayed wound healing and the active phase of scar formation can persist substantially even after wound closure. Currently, the pathophysiology of the hypertrophic scar is not completely understood. This study investigated the inflammatory response in scar tissue at week 6 post-burn injury. Methods: A porcine deep dermal partial thickness burn model was used. At week 6 post-burn, a total of 528 scar biopsies from 72 burn scars (7-8 biopsies from each scar) and 174 normal skin biopsies from 18 pigs were collected and examined histologically. Results: Microscopic inflammatory foci were identified in 17% (89/528) of scar biopsies. These microscopic inflammatory foci do not contain any irritant materials, are composed largely of polymorphonuclear cells with other inflammatory cells including multinucleate giant cells and show acute on chronic inflammatory response that has not been described previously in burn scars. Importantly, they are present in a significantly lower number in burns surgically debrided than in burns which have not been debrided. Conclusions: This study identifies microscopic inflammatory foci in the porcine scar tissue layer and recommends thorough cleaning/debriding of burned necrotic tissue in order to minimize the formation of these inflammatory foci in scar tissue. Wang X-Q, Phillips GE, Wilkie I, Greer R, Kimble RM. Microscopic inflammatory foci in burn scars: data from a porcine burn model.

Wound Repair Regen. 2009 Jul-Aug; 17(4): 548-58van den Bogaerdt AJ, van der Veen VC, van Zuijlen PP, Reijnen L, Verkerk M, Bank RA, Middelkoop E, Ulrich MMIn this work, different fibroblast-like (mesenchymal) cell populations that might be involved in wound healing were characterized and their involvement in scar formation was studied by determining collagen synthesis and processing. Depending on the physical and mechanical properties of the tissues, specific collagen cross-linking routes are followed. In skin the cross-linking of the pyridinium type is normally very low; however, in different forms of fibrosis increased levels of this type of cross-linking have been found. The enzyme lysyl hydroxylase-2b (LH-2b) plays a crucial role in this type of cross-linking. The gene expression levels of LH-2b, alpha-smooth muscle actin, and collagen types I and III were determined in dermis, subcutaneous fat, and (hypertrophic) scar tissue as well as in isolated cultured mesenchymal cells derived from these tissues, by real-time RT-polymerase chain reaction. Cultured mesenchymal cells from fat and scar tissue as well as the tissues itself showed significantly higher expression of LH-2b, alpha-SMA, and collagen type I than dermal mesenchymal cells. LH-2b-dependent pyridinium cross-linking was significantly enhanced in fat and scar tissue compared with dermis. FACS analysis was performed to characterize the fibroblast-like cells from the dermis, fat, and scar tissue. All cell populations express the distinct pattern of CD markers also expressed by mesenchymal stromal cells. Furthermore, parts of these cell populations were able to differentiate into adipocytes, chondrocytes, and osteoblasts. We conclude, therefore, that mesenchymal (stem) cells from the subcutaneous fat might be responsible for the accumulation of collagen in these scars.

J Oral Maxillofac Surg. 2009 Aug; 67(8): 1581-8Aziz SR, Rhee ST, Redai IPURPOSE: The authors review their experiences during multiple cleft surgical missions to rural Bangladesh from 2006 to 2008. A significant number of patients who underwent primary palatoplasty or cheiloplasty were of adult age or size. Adult primary cleft lip and palate repair is often more challenging than repair at the standard age of fewer than 2 years. This patient population is rarely seen in the United States, but may be treated more often by American surgeons during surgical missions to the developing world. This report discusses the experiences of the authors' treatment of cleft lips and palates in rural Bangladesh. PATIENTS AND METHODS: One hundred forty-six cleft-lip and cleft-palate patients were treated during 3 missions to rural Bangladesh, from 2006 to 2008. Thirty-three (23%) patients were of adult size, and aged 13 to 35 years. One hundred thirteen (77%) patients were aged 12 years or younger. Unilateral cleft lips were repaired with a Millard advancement-rotation technique. Bilateral cleft lips were repaired via the 1-stage procedure advocated by Mulliken and Salyer. Cleft palates were repaired using a 2-finger flap method. RESULTS: Overall, 8 of 146 patients (5.5%) had nonlife-threatening complications (infection or wound dehiscence) requiring subsequent revision surgery. The adult-sized patients had clefts of significantly increased size secondary to patient growth, as well as maxillary expansion transversely and anteriorly. Adult cleft-lip repair required significant soft-tissue dissection to close the cleft adequately, and ensure symmetry to the upper lip and alar bases. However, this procedure sometimes resulted in placement of the lip cicatrix in an anatomically disadvantageous position. In addition, with the increased transverse dimension of the adult cleft palate, tension-free 3-layer closure was difficult. Again, aggressive dissection of the soft tissue was required: the nasal and muscular layers were closed without much tension, but oral closure was often under tension, requiring the assistance of dermal biomaterials to bolster the repair. CONCLUSIONS: Patients in the developing world often have limited access to specialized health care, and may not realize that cleft lips and palates can be repaired. As a result, there is an increased incidence of unrepaired clefts in adult-sized individuals in this part of the globe. The American surgeon may encounter these patients during surgical missions. The surgeon should be prepared to repair adult patients with clefts that are significantly enlarged in all 3 dimensions. Closure will require significant soft-tissue dissection as well as the use of biomaterials as needed to repair wide cleft palates.

Surg Innov. 2009 Jun; 16(2): 181-6Decarli LA, Zorron R, Branco A, Lima FC, Tang M, Pioneer SR, Sanseverino JI, Menguer R, Bigolin AV, Gagner MObjectives. Natural orifice translumenal endoscopic surgery (NOTES) represents the first step toward scar-less surgery. The objective of this study is to evaluate early clinical results of transvaginal cholecystectomy using a new technique. Methods. Institutional review board approval was obtained and transvaginal NOTES cholecystectomy was performed in 12 women for cholelithiasis. A 2-channel videoendoscope was inserted in the abdominal cavity through a posterior colpotomy. Two 3-mm trocars were inserted deep in the umbilicus, and a 10-mm trocar was placed through the colpotomy parallel to the endoscope. Dissection was performed with endoscopic instruments combined with 3-mm laparoscopic instruments. Results. Mean operative time was 125.8 minutes. All procedures occurred without intraoperative complications or conversions, except for 1 vulvar laceration. There were no postoperative complications in the clinical follow-up. Conclusion. Transvaginal NOTES is a feasible and safe alternative for cholecystectomy in this preliminary clinical experience, allowing good cosmetic benefits and low analgesic requirement.

J Mol Cell Cardiol. 2009 Jun 25; Palatinus JA, Rhett JM, Gourdie RGRegenerative healing is the process by which injured tissues are restored to their original structure and function. Many species are capable of healing in this manner. However, in mammals the healing response in most tissues is marked by fibroblast proliferation and scar tissue deposition. While scarring contributes to efficient resolution of mammalian wounds and restoration of at least partial structural and functional support, the final result of scar formation can be more deleterious than the initial insult. This is especially true in the heart, which is sensitive to electrical heterogeneities and altered mechanical properties produced by scarring. Several therapeutic modalities promoting regeneration in skin wounds have been developed that modulate various aspects of the healing process. Targets include cytokine stimulation, control of fibroblast activation, modulation of gap junctions, and stem cell differentiation. Here, we review and compare mechanisms of injury, repair, and scarring in the skin and heart and discuss the promise and caveats of future therapies that may translate to improving repair of myocardial tissues.

Braz J Otorhinolaryngol. 2008 Nov-Dec; 74(6): 926-32Campagnolo AM, Tsuji DH, Sennes LU, Imamura RSteroids are potent inhibitors of inflammation and wound repair. Local administration of steroids directly into the larynx has been reported in many laryngeal diseases. AIM: The purpose of this study is to review related literature about the use of steroid injection in patients with benign, inflammatory and chronic vocal disease. METHODOLOGY: We performed an electronic survey in Medline database and selected clinical trials regarding steroid use in benign laryngeal diseases. RESULTS: Steroids are indicated in these situations: 1) acute inflammatory diseases, mainly when edema compromises the airways; 2) auto- immune disease with laryngeal involvement; 3) laryngeal stenosis; 4) benign lesions of the vocal folds, e.g., nodules, polyps and Reinke's edema, to reduce the inflammatory reactions before phonosurgery or in an attempt to avoid surgery; 5) In phonosurgery, aiming to reduce scarring. In this case, it could be used as a preventive measure in vocal fold scarring, or for scar treatment. CONCLUSION: Steroids may be considered an important therapeutic option in the management of many diseases, specially the inflammatory ones, associated with vocal changes.

Braz J Otorhinolaryngol. 2008 Nov-Dec; 74(6): 926-32Campagnolo AM, Tsuji DH, Sennes LU, Imamura RSteroids are potent inhibitors of inflammation and wound repair. Local administration of steroids directly into the larynx has been reported in many laryngeal diseases. AIM: The purpose of this study is to review related literature about the use of steroid injection in patients with benign, inflammatory and chronic vocal disease. METHODOLOGY: We performed an electronic survey in Medline database and selected clinical trials regarding steroid use in benign laryngeal diseases. RESULTS: Steroids are indicated in these situations: 1) acute inflammatory diseases, mainly when edema compromises the airways; 2) auto- immune disease with laryngeal involvement; 3) laryngeal stenosis; 4) benign lesions of the vocal folds, e.g., nodules, polyps and Reinke's edema, to reduce the inflammatory reactions before phonosurgery or in an attempt to avoid surgery; 5) In phonosurgery, aiming to reduce scarring. In this case, it could be used as a preventive measure in vocal fold scarring, or for scar treatment. CONCLUSION: Steroids may be considered an important therapeutic option in the management of many diseases, specially the inflammatory ones, associated with vocal changes.

Tech Coloproctol. 2009 Jul 14; Ekçi B, Gökçe OBACKGROUND: Failures of flap rotation, flap necrosis, recurrence of the disease, maceration at the incisional line and insufficient or late healing of flap corners which can be associated with ischemia appear to be the main problems associated with the closing techniques during the surgical treatment of this disease. We describe a simple, effective and incision protective repair method for excision of the pilonidal cyst. METHODS: Data from 17 (12 males and 5 females) consecutive patients who had elective surgery for chronic pilonidal sinus disease with wide excision of all the sinuses and a new flap technique closure with adipo-fascio-cutaneous flaps which was used in our series for the treatment of pilonidal sinus disease were retrospectively analyzed. RESULTS: Satisfactory results were achieved with this flap rotation technique in 17 patients. There were no flap rotation failures, flap necrosis, disease recurrence, incisional line maceration, or delayed wound healing. CONCLUSION: As a result, presented technique provides avoidance of flap necrosis, maceration on the incision and insufficient or late healing of the flap. We describe a technique which has a minimal amount of scar across the midline natal cleft and fewer flap corners resulting in a lower chance of margin necrosis.

Expert Opin Investig Drugs. 2009 Aug; 18(8): 1231-9Occleston NL, Fairlamb D, Hutchison J, O'Kane S, Ferguson MWDisfiguring scarring in the skin is an area of high medical need. Current treatments for scarring have variable or limited effectiveness and have typically not been evaluated in randomized, controlled, double-blind clinical trials. The prophylactic improvement in scar appearance, through administration of agents around the time of injury, represents a new therapeutic approach for which there are currently no registered pharmaceuticals. Extensive research into the mechanisms of scar-free and scar-forming healing has provided a robust scientific rationale for the development of avotermin (human recombinant TGF-beta3) as a potential therapeutic for the improvement of scar appearance in humans. The pioneering approach used for the clinical development of avotermin in this new indication has explained the efficacy and safety profile of avotermin in several, prospectively randomized, double-blind clinical studies in human volunteers and patients. These studies, which show a clear translation from preclinical efficacy models to the clinical environment, have shown that prophylactic scar improvement is pharmaceutically achievable. It is anticipated that therapeutics such as avotermin, with a sound mechanistic basis and proof of effectiveness in suitably robust clinical trials, will be available to meet the needs of patients in the foreseeable future.

Pediatr Nephrol. 2009 Jul 15; Sekerli E, Katsanidis D, Vavatsi N, Makedou A, Gatzola MUrinary tract infection is a common bacterial disease that presents during childhood and may lead to renal scarring. Several studies have shown a strong association between the angiotensin converting enzyme (ACE) deletion polymorphism and renal scarring in children with vesicoureteric reflux (VUR). The purpose of this study was to investigate the possible correlation between the ACE deletion polymorphism and renal scarring in 186 children with urinary tract infection (UTI), of whom 90 were renal scar positive and 96 were renal scar negative. The control group consisted of 129 children with no UTI. Renal scars were diagnosed by means of (99m)Tc-dimercapto-succinic acid scans, and ACE genotypes were determined as II, ID, and DD by PCR analyses. The ACE genotype distribution was 10% II, 67% ID, and 23% DD in the renal scar-positive group, 18% IotaIota, 42% ID, and 40% DD in the renal scar-negative group, and 22% II, 47% ID, and 31% DD in the control group. No correlation was found between the DD genotype and renal scar formation in children with UTI. The same results were obtained following strafication of the patients by VUR and age of the first urinary tract infection. In conclusion, the results of this study suggest that the DD genotype is not an independent risk factor for renal scarring in children with UTI.

Ann Plast Surg. 2009 Jul 13; Cárdenas-Camarena LThe techniques of reduction mammoplasty are multiple and varied. Each one has advantages and disadvantages. With any of them, full preservation of vascularity and sensitizing of the nipple-areola complex (NAC) should be sought, as well as functionality of the breast. We present our 15 years' experience using the superolateral dermoglandular pedicle, a technique that fully preserves the integrity of the breast. During that 15-year period, we operated on 702 breasts in 356 patients, using the superolateral dermoglandular pedicle, with the NAC requiring a migration of 5 to 16 cm (mean: 9.2 cm), having resected breast tissue between 300 and 1380 g, (average: 660 g). The technique was used in women between 16 and 63 years of age (average 37), who wanted breast reduction and who required a migration of the NAC greater than 5 cm.We had minor complications consisting of wound dehiscence (5.9%), scar hyperpigmentation (3.9%), fat necrosis (3.8%), hypertrophic scarring (3.1%), alterations in sensitivity (2.27%), and keloid scarring (0.5%). We had 9 cases of necrosis of the NAC (1.28%), of which 7 were partial (0.99%) and 2 were total (0.28%). Satisfaction with the results was 94%.The technique of reduction mammoplasty with a superolateral dermoglandular pedicle has been used in mammary hypertrophy and gigantomasty with excellent results. Its design is simple, its performance easy, and its aesthetic results are highly reproducible. The position of the pedicle allows full preservation of the vascularity, sensitivity, and functionality of the breast, and is therefore a highly recommendable technique.

Pain Med. 2009 Jul 6; Tamimi MA, McCeney MH, Krutsch JABSTRACT Introduction. Pulsed radiofrequency (PRF) current applied to nerve tissue to treat intractable pain has recently been proposed as a less neurodestructive alternative to continuous radiofrequency lesioning. Clinical reports using PRF have shown promise in the treatment of a variety of focal, neuropathic conditions. To date, scant data exist on the use of PRF to treat myofascial and neuromatous pain. Methods. All cases in which PRF was used to treat myofascial (trigger point) and neuromatous pain within our practice were evaluated retrospectively for technique, efficacy, and complications. Trigger points were defined as localized, extremely tender areas in skeletal muscle that contained palpable, taut bands of muscle. Results. Nine patients were treated over an 18-month period. All patients had longstanding myofascial or neuromatous pain that was refractory to previous medical management, physical therapy, and trigger point injections. Eight out of nine patients experienced 75-100% reduction in their pain following PRF treatment at initial evaluation 4 weeks following treatment. Six out of nine (67%) patients experienced 6 months to greater than 1 year of pain relief. One patient experienced no better relief in terms of degree of pain reduction or duration of benefit when compared with previous trigger point injections. No complications were noted. Discussion. Our review suggests that PRF could be a minimally invasive, less neurodestructive treatment modality for these painful conditions and that further systematic evaluation of this treatment approach is warranted.

Aesthet Surg J. 2009 May-Jun; 29(3): 180-8van der Lei B, Cromheecke M, Hofer SOBACKGROUND: Over the last two decades, short scar facelifts, often referred to as "mini" facelifts, have gained popularity. We use a purse-string reinforced (PRS) superficial musculoaponeurotic system rhytidectomy (SMASectomy) shortscar facelift that combines a SMASectomy in the vertical direction and suspension sutures in order to improve structural facial support. In the case of visible platysma bands and/or local fat deposition, liposuction (frequently followed by an anterior plastysmaplasty procedure) was added to correct features that are not consistently correctable using only a short scar facelift. OBJECTIVE: This study retrospectively analyzes our experience with a new type of short scar facelift technique that combines both a superficial musculoaponeurotic system rhytidectomy (SMAS-ectomy) and suspension sutures with a thorough approach to the anterior surface of the neck. METHODS: Over a period of three years, the PRS short scar facelift was performed in 137 patients with a mean age of 55 years (range 23-79 years). In almost half of the patients, the PRS short scar facelift was preceded by a separate treatment of the anterior neck contour by liposuction (67/137 patients; 49%). In two-thirds of these patients (42/67 patients), this liposuction was followed by an anterior plastymaplasty. RESULTS: Most patients (129/137; 94%) were satisfied or very satisfied with their results at the end of the follow-up period. Eight patients were not satisfied: five because of higher expectations, two because of insufficient improvement of the plastysma bands (which had not been treated by a plastysmaplasty procedure), and one because of the improper recognition of midface sagging (which had not been treated and was not properly discussed preoperatively). In the case of plastysma bands, platysmaplasty (n = 42) did improve the presence of these bands. There were no major complications in this series: 1 case had temporary neuropraxia of a buccal branch, which resolved after two months; two cases had hematoma, requiring evacuation on the outpatient clinic after one week; two cases with traction dimpling in the neck over the sternocleidomastoid region required late surgical revision; and one case had hypertrophic scarring in the preauricular area. CONCLUSIONS: The PRS technique is a short scar facelift technique that is both simple and safe. Complications are uncommon and usually minor. However, in the presence of platysma bands and/or local fat deposition, an anterior neck procedure-liposuction and/or anterior platysmaplasty-should be incorporated in order to optimize the results.

Reprod Domest Anim. 2009 Jul 7; Alves BC, Hossepian de Lima VF, Moreira-Filho CContents Sex pre-selection of bovine offsprings has commercial relevance for cattle breeders and several methods have been used for embryo sex determination. Polymerase chain reaction (PCR) has proven to be a reliable procedure for accomplishing embryo sexing. To date, most of the PCR-specific primers are derived from the few single-copy Y-chromosome-specific gene sequences already identified in bovines. Their detection demands higher amounts of embryonic genomic material or a nested amplification reaction. In order to circumvent this, limitation we searched for new male-specific sequences potentially useful in embryo sexing using random amplified polymorphic DNA (RAPD) analysis. Random amplified polymorphic DNA (RAPD) assay reproducibility problems can be overcome by its conversion into Sequence Characterized Amplified Region (SCAR) markers. In this work, we describe the identification of two bovine male-specific markers (OPC16(323) and OPF10(1168)) by means of RAPD. These markers were successfully converted into SCARs (OPC16(726) and OPF10(984)) using two pairs of specific primers.Furthermore, inverse PCR (iPCR) methodology was successfully applied to elongate OPC16(323) marker in 159% (from 323 to 837 bp). Both markers are shown to be highly conserved (similarity >/=95%) among bovine zebu and taurine cattle; OPC16(323) is also highly similar to a bubaline Y-chromosome-specific sequence. The primers derived from the two Y-chromosome-specific conserved sequences described in this article showed 100% accuracy when used for identifying male and female bovine genomic DNA, thereby proving their potential usefulness for bovine embryo sexing.

J Neurosci Methods. 2009 Jul 8; Jaroch DB, Ward MP, Chow EY, Rickus JL, Irazoqui PPChronic recording electrodes are a vital tool for brain research and neural prostheses. Despite decades of advances in recording technology, probe structures and implantation methods have changed little over time. Then as now, compressive insertion methods require probes to be constructed from hard, stiff materials, such as silicon, and contain a large diameter shank to penetrate the brain, particularly for deeper structures. The chronic presence of these probes results in an electrically-isolating glial scar, degrading signal quality over time. This work demonstrates a new magnetic tension-based insertion mechanism that allows for the use of soft, flexible, and thinner probe materials, overcoming the materials limitations of modern electrodes. Probes are constructed from a sharp magnetic tip attached to a flexible tether. A pulsed magnetic field is generated in a coil surrounding a glass pipette containing the electrode. The applied field pulls the electrode tip forward, accelerating the probe into the neural tissue with a penetration depth that is calibrated against the charge voltage. Mathematical modeling and agar gel insertion testing demonstrate that the electrode can be implanted to a predictable depth given system specific parameters. Trial rodent implantations resulted in discernible single-unit activity on one of the probes. The current prototype demonstrates the feasibility of a tension based, magnetically driven implantation system and opens the door to a wide variety of new minimally invasive probe materials and configurations.

J Orthop Res. 2009 Jul 14; Qin L, Wang L, Wan-Nar Wong M, Wen C, Wang G, Zhang G, Chan KM, Cheung WH, Leung KSHealing at the osteotendinous junction (OTJ) is challenging in orthopedic surgery. The present study aimed to test extracorporeal shockwave (ESW) in treatment of a delayed OTJ healing. Twenty-eight rabbits were used for establishing a delayed healing (DH) model at patella-patellar-tendon (PPT) complex after partial patellectomy for 4 weeks and then were divided into DH and ESW groups. In the ESW group, a single ESW treatment was given at postoperative week 6 to the PPT healing complex. The samples were harvested at week 8 and 12 for radiographic and histological evaluations with seven samples for each group at each time point. Micro-CT results showed that new bone volume was 1.18 +/- 0.61 mm(3) in the ESW group with no measurable new bone in the DH group at postoperative week 8. Scar tissue formed at the OTJ healing interface of the DH group, whereas ESW triggered high expression of VEGF in hypertrophic chondrocytes at week 8 and regeneration of the fibrocartilage zone at week 12 postoperatively. The accelerated osteogenesis could be explained by acceleration of endochondral ossification. In conclusion, ESW was able to induce osteogenesis at OTJ with delayed healing with enhanced endochondral ossification process and regeneration of fibrocartilage zone. These findings formed a scientific basis to potential clinical application of ESW for treatment of delayed OTJ healing. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Anticancer Res. 2009 Jul; 29(7): 2645-53Bremke M, Barth PJ, Sesterhenn AM, Budach V, Engenhart-Cabillic R, Werner JABACKGROUND: Definitive chemoradiation is a well-established option in the treatment of locally advanced squamous cell carcinoma of the head and neck. The intention of this study was to evaluate its efficacy on cervical lymph node metastases in a prospective study after a standardized protocol for chemoradiation (CRT) and histopathological evaluation, respectively. PATIENTS AND METHODS: The data of 25 patients (10 oropharynx, 15 hypopharynx) who received planned neck dissection after definitive chemoradiation for UICC stage IV carcinomas of the pharynx were analyzed. All patients were sonomorphologically staged positive for lymph nodes (3 patients: N1; 2 patients N2a; 7 patients N2b; 9 patients N2c and 4 patients N3). A neck dissection was carried out 8.9+/-1.5 weeks (range 6-13) post treatment. The specimens obtained from the different neck levels were histologically examined for viable tumour cells. RESULTS: Local control was achieved in 100% of all patients on endoscopy 9 weeks after the chemoradiation. In 14/25 patients (56%), still viable tumour tissue was found in the neck dissection (ND) specimen. Only one of these 14 patients (7%) was deemed suspicious for residual lymphadenopathy from clinical and diagnostic findings at re-staging after chemoradiation, the others were staged yN0. Postsurgical complications occurred in six patients (24%) such as bleeding and prolonged wound healing in one patient each and functional deficits in an additional four patients. One patient developed a scar recurrence seven months after surgery. CONCLUSION: Based on these findings, the ultimate efficacy of primary CRT should not be judged 8-10 weeks after the treatment. Therefore planned neck dissection should be performed no earlier than 12 weeks after primary CRT.

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1088-92Diao JS, Zhang X, Ren J, Zeng HF, Liu B, Ma FC, Wang YM, Yang XT, Guo SZ, Xia WOBJECTIVE: To investigate the effects of Notch signaling on scars in a rabbit ear model of hypertrophic scarring. METHODS: The hypertrophic scar of rabbits' ears was reproduced. The left rabbit's ear wounds as the N-[N-(3,5-difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) treated group were treated intradermally with the gamma-secretase inhibitor DAPT to inhibit the activation of Notch at 1, 3, 7 and 14 day time points. The right ears as the control group were treated with normal saline at the same time points. Experimental and control wounds were harvested on days 14, 21, 28 and 35 post wounding, and then examined histologically to quantify hypertrophic index and fibroblasts. The expression of epidermal differentiation markers-keratin 14 (K14), keratin 19 (K19), Involucrin and Notch downstream molecules-P21, P63 were examined and analyzed with immunohistochemistry staining. RESULTS: Both hypertrophic index (1.93 +/- 0.32, 1.82 +/- 0.36, 1.79 +/- 0.25) and number of fibroblasts [(4.08 +/- 0.88), (3.30 +/- 0.53), (3.19 +/- 0.73) x 10(3)/mm(2)] in the DAPT treated group were significantly reduced on days 21, 28 and 35, compared with the control group [2.56 +/- 0.29, 2.61 +/- 0.30, 2.58 +/- 0.39, and (5.45 +/- 0.99), (4.80 +/- 1.13), (4.43 +/- 1.17) x 10(3)/mm(2), all P < 0.01)]. The K19, K14 and P63 increased their expression in the DAPT treated group (28.6% +/- 5.7%, 53.1% +/- 4.5%, 57.0% +/- 5.8%) relative to the control group (10.1% +/- 2.8%, 30.8% +/- 4.9%, 16.5% +/- 2.2%, all P < 0.01) on day 14 post wounding, while the Involucrin and P21 decreased their expression in the DAPT treated group (12.3% +/- 1.9%, 11.0% +/- 1.7%) relative to the control group (29.3% +/- 4.6%, 44.3% +/- 3.5%, both P < 0.01). CONCLUSION: Inactivation of Notch signaling will inhibit scar epidermis to over-differentiation, and thereby inhibit proliferation of hypertrophic scars in the rabbit ears.

BMC Neurol. 2009 Jul 15; 9(1): 32Buss A, Pech K, Kakulas BA, Martin D, Schoenen J, Noth J, Brook GAABSTRACT: BACKGROUND: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord. METHODS: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. RESULTS: In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan. Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots. CONCLUSIONS: NG2 and phosphacan were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration. Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration. The present data points to the importance of such correlative investigations for demonstrating the clinical relevance of experimental data.

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1088-92Diao JS, Zhang X, Ren J, Zeng HF, Liu B, Ma FC, Wang YM, Yang XT, Guo SZ, Xia WOBJECTIVE: To investigate the effects of Notch signaling on scars in a rabbit ear model of hypertrophic scarring. METHODS: The hypertrophic scar of rabbits' ears was reproduced. The left rabbit's ear wounds as the N-[N-(3,5-difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) treated group were treated intradermally with the gamma-secretase inhibitor DAPT to inhibit the activation of Notch at 1, 3, 7 and 14 day time points. The right ears as the control group were treated with normal saline at the same time points. Experimental and control wounds were harvested on days 14, 21, 28 and 35 post wounding, and then examined histologically to quantify hypertrophic index and fibroblasts. The expression of epidermal differentiation markers-keratin 14 (K14), keratin 19 (K19), Involucrin and Notch downstream molecules-P21, P63 were examined and analyzed with immunohistochemistry staining. RESULTS: Both hypertrophic index (1.93 +/- 0.32, 1.82 +/- 0.36, 1.79 +/- 0.25) and number of fibroblasts [(4.08 +/- 0.88), (3.30 +/- 0.53), (3.19 +/- 0.73) x 10(3)/mm(2)] in the DAPT treated group were significantly reduced on days 21, 28 and 35, compared with the control group [2.56 +/- 0.29, 2.61 +/- 0.30, 2.58 +/- 0.39, and (5.45 +/- 0.99), (4.80 +/- 1.13), (4.43 +/- 1.17) x 10(3)/mm(2), all P < 0.01)]. The K19, K14 and P63 increased their expression in the DAPT treated group (28.6% +/- 5.7%, 53.1% +/- 4.5%, 57.0% +/- 5.8%) relative to the control group (10.1% +/- 2.8%, 30.8% +/- 4.9%, 16.5% +/- 2.2%, all P < 0.01) on day 14 post wounding, while the Involucrin and P21 decreased their expression in the DAPT treated group (12.3% +/- 1.9%, 11.0% +/- 1.7%) relative to the control group (29.3% +/- 4.6%, 44.3% +/- 3.5%, both P < 0.01). CONCLUSION: Inactivation of Notch signaling will inhibit scar epidermis to over-differentiation, and thereby inhibit proliferation of hypertrophic scars in the rabbit ears.

PLoS One. 2009; 4(7): e6227Desclaux M, Teigell M, Amar L, Vogel R, Gimenez Y Ribotta M, Privat A, Mallet JBACKGROUND: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both GFAP and vimentin presented lower levels of glial reactivity in vivo, significant axonal regrowth and improved functional recovery in comparison with wild-type mice after spinal cord hemisection. From these results, our objective was to develop a novel therapeutic strategy for axonal regeneration, based on the targeted suppression of astroglial reactivity and scarring by lentiviral-mediated RNA-interference (RNAi). METHODS AND FINDINGS: In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv-shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes, the use of these vectors resulted in a specific, stable and highly significant decrease in the corresponding protein levels. In a second model -- scratched primary cultured astrocytes -- Lv-shGFAP, alone or associated with Lv-shVIM, decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic coculture model, cortical neurons displayed higher survival rates and increased neurite growth when cultured with astrocytes in which GFAP and vimentin had been invalidated by lentiviral-mediated RNAi. CONCLUSIONS: Lentiviral-mediated knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for modulating reactive gliosis and monitoring neuron/glia interactions. Thus, manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a promising therapeutic strategy for increasing glial permissiveness and permitting axonal regeneration after central nervous system lesions.

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1093-7Tao L, Liu JY, Li SR, Dai X, Li ZOBJECTIVE: To validate whether STAT1 paticipated in the process of CTGF-induced proliferation and differentiation of human hypertrophic scar fibroblast (hHSF) on account of past research. METHODS: To cultivate hHSF with 6 patients' hypertrophic scar specimens together. Electrophoretic mobility shift assay (EMSA) was used to verify binding ability between DNA and STAT1 with the stimulus of different concertration CTGF (0, 5, 7.5, 10, 15 ng/ml) at 45th min and the stimulus of 10 ng/ml CTGF at different phase point (0, 10, 20, 30, 45, 60, 90, and 120 min). We divided cells into CTGF group, STAT1 ASODN group. STAT1 ASODN + CTGF group. control group. And MTT was used to detect the proliferation of hHSF on days1, 2 and 3, and RT-PCR to detect alpha-smouth muscle actin mRNA to follow the differentiation. RESULTS: EMSA showed that the binding ability between STAT1 and DNA depended on the concentration of CTGF and peaked with the stimulation of 10ng/ml CTGF. And at the same time, it peaked at 45 - 60 min with 10 ng/ml CTGF. MTT showed that cell proliferation of CTGF group was much higher than that of control group (all P < 0.05). And those of STAT1 ASODN group and STAT1 ASODN + CTGF group were much lower than those of control group and CTGF group (all P < 0.05). RT-PCR showed that differentiation activation from fibroblast to myofibroblast of CTGF group, STAT1 ASODN group, STAT1 ASODN + CTGF group and control group were 0.78 +/- 0.08, 0.38 +/- 0.09, 0.76 +/- 0.10, and 0.40 +/- 0.12, respectively. Differentiation activation of STAT1 ASODN group and control group were much lower than those of CTGF group and STAT1 ASODN + CTGF group (all P < 0.05). CONCLUSION: STAT1 ASODN is important in the process of proliferation of hHSF and it blocks the stimulation of CTGF on hHSF proliferation. The above result revealed that STAT1 participates in the process of hHSF proliferation induced by connective tissue growth factor.

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1093-7Tao L, Liu JY, Li SR, Dai X, Li ZOBJECTIVE: To validate whether STAT1 paticipated in the process of CTGF-induced proliferation and differentiation of human hypertrophic scar fibroblast (hHSF) on account of past research. METHODS: To cultivate hHSF with 6 patients' hypertrophic scar specimens together. Electrophoretic mobility shift assay (EMSA) was used to verify binding ability between DNA and STAT1 with the stimulus of different concertration CTGF (0, 5, 7.5, 10, 15 ng/ml) at 45th min and the stimulus of 10 ng/ml CTGF at different phase point (0, 10, 20, 30, 45, 60, 90, and 120 min). We divided cells into CTGF group, STAT1 ASODN group. STAT1 ASODN + CTGF group. control group. And MTT was used to detect the proliferation of hHSF on days1, 2 and 3, and RT-PCR to detect alpha-smouth muscle actin mRNA to follow the differentiation. RESULTS: EMSA showed that the binding ability between STAT1 and DNA depended on the concentration of CTGF and peaked with the stimulation of 10ng/ml CTGF. And at the same time, it peaked at 45 - 60 min with 10 ng/ml CTGF. MTT showed that cell proliferation of CTGF group was much higher than that of control group (all P < 0.05). And those of STAT1 ASODN group and STAT1 ASODN + CTGF group were much lower than those of control group and CTGF group (all P < 0.05). RT-PCR showed that differentiation activation from fibroblast to myofibroblast of CTGF group, STAT1 ASODN group, STAT1 ASODN + CTGF group and control group were 0.78 +/- 0.08, 0.38 +/- 0.09, 0.76 +/- 0.10, and 0.40 +/- 0.12, respectively. Differentiation activation of STAT1 ASODN group and control group were much lower than those of CTGF group and STAT1 ASODN + CTGF group (all P < 0.05). CONCLUSION: STAT1 ASODN is important in the process of proliferation of hHSF and it blocks the stimulation of CTGF on hHSF proliferation. The above result revealed that STAT1 participates in the process of hHSF proliferation induced by connective tissue growth factor.

Biomed Tech (Berl). 2009 Jul 14; Venhaus M, Behn C, Freitag L, Zimmermann KAbstract This article investigates the mechanics of balloon dilatation in the treatment of bronchotracheal stenosis. The "scar stricture"-type stenosis examined in this paper is typically dilated manually, using a dilatation balloon. If indicated, this is followed by stent implantation. The selection of the stent with proper characteristics is performed empirically, based on personal experience and preference. In order to optimize the therapeutic outcome, however, it is necessary to match the stent with the stress-strain properties of the stenosis, which are not determined during manual balloon dilatation. The objective is to utilize models to experimentally and theoretically establish the correlation between the pressure/volume curve measured during the dilatation and the stress-strain properties of the stenosis, taking into account that during dilatation of scar strictures the balloon is only partially compressed, as it extends beyond both ends of the stenosis. Experiments are carried out using stenosis models with various extensibilities and lengths. As expected, more hardened stenosis resulted in steeper pressure/volume curves during the dilatation. On the other hand, the comparison between stenosis of equal extensibilities, but different length, showed an initially unexpected larger distension of the shorter stenosis, at equal pressure increases. This is caused by the fact that the margins of the stenosis are allowed more time to distend, compared to the central areas of the stenosis. The term "effect of margin expansion" was introduced to describe this behavior. The modeling of the dilatation process is based on the equilibrium conditions of cut-free balloon portions. The balloon/stenosis system is divided into three areas with different characteristics: (1) the proximal and distal area of the balloon outside the stenosis; (2) the area of contact between the balloon and the stenosis; and (3) the transition area between (1) and (2). Numerical simulations of the balloon dilatation confirm the conclusions from the experimental results and the theoretical considerations regarding the correlation between the pressure/volume curve of the dilatation and the stress-strain properties of the stenosis.

Lasers Med Sci. 2009 Jul 15; Elsaie ML, Nouri K, Vejjabhinanta V, Patricia Rivas M, Magaly Villafradez-Diaz L, Martins A, Rosso RThe purpose of this study is to evaluate the efficacy of tattoo removal using topical imiquimod 5% cream in conjunction with the 1,064-nm Nd:YAG laser. This procedure for tattoo removal will be compared to laser treatment alone, which is the standard for cosmetic removal of tattoos. Previous studies have linked partial tattoo removal to imiquimod application in a guinea pig model. Methods: This was a small-sized, double-blinded, placebo-controlled trial with patients with Fitzpatrick skin types I-IV (light skin) who were 18-65 years of age. The patients were required to have had two tattoos of similar age and dark blue or black in color in areas that can be covered by clothing. There were four visits in total, with laser treatment and photography being performed on the first visit. Laser settings were with 1,064-nm Nd:YAG with a 10-ns pulse, 3-mm spot size, and 4 J of energy, a standard laser used for tattoo removal. During the second visit, tattoos were randomized and chosen to receive either the laser-imiquimod treatment course or laser-vehicle cream treatment. The patients returned 1 month after the completion of cream application (week #10) and 2 months after the completion of treatment with cream (week #14) for final evaluation and photographing. Results: Three patients were enrolled in this study. All of them are Fitzpatrick skin type IV. All of the patients were compliant with the drug application and have good tolerability with only mild pruritus without changing of vascularity or pigmentation. None of the patients had ulceration or scar development during the cream application. Conclusions: imiquimod plus laser therapy demonstrated a more favorable outcome when evaluated by the investigators or subjects. The mean scores for tattoo clearance from baseline to 2 months after completion of treatment with 5% imiquimod cream versus placebo cream were 4.3 versus 2.7 as rated by investigators and 4.7 versus 2.3 as rated by subjects. No textural changes were observed after therapy and were not shown to be different between the two groups. Further large-scale studies are important in developing a role for the use of imiqumod in laser-assisted tattoo removal.

Spinal Cord. 2009 Jul 14; Onose G, Anghelescu A, Muresanu DF, Padure L, Haras MA, Chendreanu CO, Onose LV, Mirea A, Ciurea AV, El Masri WS, von Wild KRStudy design:Literature review.Objectives:To review the main published current neuroprotection research trends and results in spinal cord injury (SCI).Setting:This paper is the result of a collaboration between a group of European scientists.Methods:Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies.Results:There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'gamma-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin gene-including neurotransmitter-receptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions.Conclusion:The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.Spinal Cord advance online publication, 14 July 2009; doi:10.1038/sc.2009.52.

Aesthetic Plast Surg. 2009 Jul 14; Pereira LH, Sterodimas ABACKGROUND: During the last decades transaxillary breast augmentation (TBA) has gained worldwide acceptance. Breast augmentation via transaxillary access endoscopically assisted in the subglandular, subfascial, and submuscular planes has been previously described. Although TBA is a well-studied procedure, few reports exist concerning the subfascial plane of implant insertion and none exist comparing the three different planes of insertion by TBA. METHODS: A perspective study to evaluate the outcomes, complications, and patient satisfaction of TBA using the three different planes of implant insertion was performed during 2004-2005. Fifty-three patients fulfilled the inclusion criteria. They were randomly divided into three groups corresponding to the three planes of silicone insertion. All patients had a silicone texturized implant that ranged from 190 to 300 cc. Overall satisfaction with the breast appearance after TBA was rated on a scale of 1-5, where 1 is poor, 2 is fair, 3 is good, 4 is very good, and 5 is excellent. The evaluation was made at the follow-up times of 6 months and 3 years. RESULTS: There were 18 patients enrolled for the subcutaneous TBA (Group A), 18 for the subfascial TBA (Group B), and 17 for the submuscular TBA (Group C). Axillary incision-related complications occurred in 9% of the patients and included formation of a hypertrophic scar and small-wound dehiscence. There was no hematoma formation and no case of infection. There was one patient from Group A who developed seroma and was treated conservatively. Twenty-seven months postoperatively the same patient developed Baker III capsule contracture, which required silicone implant replacement in the subfascial plane. One case of stretch marks in a young nulliparous woman from Group B did not need treatment. One patient from Group A underwent implant exchange because of implant size dissatisfaction. Three patients in Group C had mild distortion of the implant during pectoral contracture. A meta-analysis of patient satisfaction 6 months and 3 years after TBA is presented. CONCLUSION: Transaxillary breast augmentation provides consistent, satisfactory results with ease of dissection, when properly indicated. Although the subfascial augmentation mammaplasty has all the advantages of the subpectoral and subglandular augmentation mammaplasties and eliminates the disadvantages of increased postoperative discomfort, implant visibility, and distortion, patients of all three groups had similar rates of satisfaction. Further follow-up is needed in order to compare the long-term effects of the three different planes of insertion.

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009 Jun; 23(6): 713-7Yuan J, Li T, Qi SOBJECTIVE: To investigate the inhibitory effect of Col I A1 antisense oligodeoxyneucleotide (ASODN) transfection mediated by cationic liposome on Col I A1 expression in human hypertrophic scar fibroblasts. METHODS: Scar tissue was obtained from volunteer donor. Human hypertrophic scar fibroblasts were cultured by tissue block method. The cells at passage 4 were seeded in a 6 well cell culture plate at 32.25 x 10(4) cells/well, and then divided into 4 groups: group A, liposome and Col I A1 ASODN; group B, Col I A1 ASODN; group C, liposome; group D, blank control. At 8 hours, 1, 2, 3 and 4 days after transfection, total RNA of the cells were extracted, the expression level of Col I A1 mRNA was detected by RT-PCR, the Col I A1 protein in ECM was extracted by pepsin-digestion method, its concentration was detected by ELISA method. RESULTS: Agarose gel electrophoresis detection of amplified products showed clear bands without occurrence of indistinct band, obvious primer dimmer and tailing phenomenon. Relative expression level of Col I A1 mRNA: at 8 hours after transfection, group A was less than groups B, C and D (P < 0.05), and groups B and C were less than group D (P < 0.05), and no significant difference was evident between group B and group C (P > 0.05); at 1 day after transfection, groups A and B were less than groups C and D (P < 0.05), and there was no significant difference between group A and group B, and between group C and group D (P > 0.05 ); at 2 days after transfection, there were significant differences among four groups (P < 0.05); at 3 and 4 days after transfection, group A was less than groups B, C and D (P < 0.05), group B was less than groups C and D (P < 0.05), and no significant difference was evident between group C and group D (P > 0.05). Concentration of Col I protein: at 8 hours after transfection, group A was less than groups B, C and D (P < 0.05), groups B and C were less than group D (P < 0.05), and no significant difference was evident between group B and group C (P > 0.05); at 1 day after transfection, significant differences were evident among four groups (P < 0.05); at 2, 3 and 4 days after tranfection, groups A and B were less than groups C and D (P < 0.05), and no significant difference was evident between group A and group B (P > 0.05). CONCLUSION: Col I A1 ASODN can inhibit mRNA and protein expression level of Col I A1. Cationic liposome, as the carrier, can enhance the inhibition by facilitating the entry of ASODN into cells and introducing ASODN into cell nucleus.

Nanomed. 2009 Jul; 4(5): 531-540Bellucci S, Chiaretti M, Cucina A, Carru G, Chiaretti AAim: We evaluated the effect of buckypaper (BP) on cancer and primary cell lines in vitro and in vivo in laboratory rats. BP is an innovative material with interesting physical/chemical properties that has possible pharmacological and prosthetic employment. Given that precautions need to be taken where carbon nanotubes are injected into human body for drug delivery, as contrast agent-carrying entities for MRI or as the material of a new prosthesis generation, we assessed the toxicity of BP carbon nanotubes. BP has structural resemblance to asbestos, whose toxicity has been linked to cancer. Results: BP decreased proliferation of human colorectal, breast and leukemic cancer cell lines in vitro. However, BP had no effect on the proliferation and viability of normal human arterial smooth muscle cells and human dermal fibroblasts in vitro. in vivo, BP induced a moderate inflammatory reaction but had no mutagenic effects. After BP implantation the animals showed an inflammatory reaction followed 2 weeks later by a cicatrization reaction with the organization and fibrosis of the scar. Conclusion: These results show a low toxicity of BP both in vitro and in vivo.

J Mol Cell Cardiol. 2009 Jun 29; Shamhart PE, Meszaros JGCardiac remodeling is accelerated during pathological conditions and several anabolic and catabolic regulators work in concert to repair the myocardium and maintain its functionality. The fibroblasts play a major role in this process via collagen deposition as well as supplying the degradative matrix metalloproteinases. During the more acute responses to a myocardial infarction (MI) the heart relies on a more aggressive wound healing sequence that includes the myofibroblasts, specialized secretory cells necessary for infarct scar formation and thus, rescue of the myocardium. The activated fibroblasts and myofibroblasts deposit large amounts of fibrillar collagen during the post-MI wound healing phase, type I and III collagen are the most abundant collagens in the heart and they maintain the structural integrity under normal and disease states. While collagen I and III have been the traditional focus of the myocardial matrix, recent studies have suggested that the non-fibrillar collagens (types IV and VI) are also deposited during pathological wound healing and may play key roles in myofibroblast differentiation and organization of the fibrillar collagen network. This review highlights the potential roles of the non-fibrillar collagens and how they work in concert with the fibrillar collagens mediate myocardial remodeling.