Acne Scars

BMC Infect Dis. 2009 Jun 26; 9(1): 100Ellertsen LK, Storla DG, Diep LM, Brokstad KA, Wiker HG, Hetland GABSTRACT: BACKGROUND: It is still a matter of debate whether there is an association between infection with Mycobacterium tuberculosis (M. tuberculosis) and allergy. Previously, we have shown higher levels of specific IgE to different inhalant allergens and total IgE in tuberculosis (TB) patients compared to controls. The objectives of this study were to evaluate a possible change in allergic sensitisation after successful TB treatment and to confirm the finding of our previous study of enhanced allergic sensitisation in TB patients compared to controls in a more controlled setting. Additionally, we wanted to determine the cytokine profile in the same groups and finally to evaluate the association between Bacillus Calmette-Guerin vaccination (BCG) scar and allergic sensitisation among the controls. METHODS: Sera were analysed for specific IgE to inhalant allergens (Phadiatop) and total IgE by the use of ImmunoCAP 1000 (Pharmacia Diagnostics). Thirteen different cytokines were also analysed in the sera by multiplex bead immunoassay (Luminex 100, Luminex Corporation), and clinical symptoms of allergy and BCG scar were reported in a questionnaire. RESULTS: A reduction in levels of specific and total IgE were observed after successful TB treatment. TB patients also had higher levels of specific and total IgE compared to healthy controls. Both interleukin (IL)-6 and interferon (IFN)gamma were higher in tuberculosis patients compared to healthy controls. The levels of IL-6 were reduced after successful tuberculosis treatment. The presence of a BCG scar was associated with a reduced risk of developing allergic sensitisation. CONCLUSIONS: We observed a reduced level of allergic sensitisation after successful TB treatment. TB patients seem to be more allergically sensitised than healthy controls confirming our previous finding. Furthermore, we observed an inverse association between allergic sensitisation and visible BCG scar, which adds additional support to the hygiene hypothesis.

J Burn Care Res. 2009 Jun 5; Grishkevich VMThe treatment of postburn contractures of perineum remains a complex and an unsolved problem. Fourteen patients were operated. According to our observations, the perineum contracture can have two formations: (a) transverse scar folds formed between both the thighs and (b) obliteration of perineum by scar tissues. The first type, most common, is successfully eliminated by using local trapezoid flaps. The flaps are prepared from the divided sheets and adjacent tissues on both inner thighs' surfaces. The flaps are performed by cross-incisions of the fold; several pairs of adipose-scar flaps are formed. Because of the crescent shape of the fold, the flaps acquire a trapezoid shape. Then, they are transposed toward each other without rotation, doubling the surface of maximum tension thus eliminating the contracture completely. This technique allows releasing the contracture without skin grafting. The flaps are 4 to 5 cm wide, and they contain subcutaneous fat layer and have no sharp angles. All this assures stable circulation and prevents necrosis, flap loss, and contracture recurrence.

Acta Psychiatr Scand. 2009 May 29; Lloyd AJ, Moore PB, Cousins DA, Thompson JM, McAllister VL, Hughes JH, Ferrier IN, Young AHObjective: We aimed to quantify both load and regional distributions of hyperintensities on magnetic resonance imaging (MRI) in prospectively verified euthymic bipolar patients and matched controls. Method: Cerebral hyperintensities on T2, proton density and fluid-attenuated inversion recovery (FLAIR) MRI were compared between 48 bipolar and 47 control subjects using semi-quantitative rating scales. Results: Bipolar subjects had more severe frontal deep white matter lesions (DWML). Hyperintensity load was independent of age in bipolar patients but increased with age in controls. Global prevalence and severity of hyperintensities did not differ between groups. Exploratory analysis showed DWML in excess in the left hemisphere in bipolar subjects but not in controls. Conclusion: Findings are consistent with clinical, particularly some neurocognitive, features of bipolar disorder and implicate fronto-subcortical circuits in its neurobiology. They more probably reflect a trait abnormality or illness scar rather than a mood state-dependent finding. Processes other than ageing and vascular factors may underlie their development.

Colorectal Dis. 2009 Apr 13; Brunner W, Schirnhofer J, Waldstein-Wartenberg N, Frass R, Weiss HAim: On the way to "no-scar" techniques we developed a novel method for colorectal resection utilizing three intraumbilical trocars which results in a non-visible postoperative scar. Methods: Two female patients (Age: 56a, 42a) underwent laparoscopic colorectal resection for diverticulitis and infiltrating endometriosis of the rectosigmoid colon, respectively. The entire operation was carried out transumbilically following the standardized principles of colorectal resection. Results: The operative time was 110min and 180min, respectively. No intraoperative adverse events or significant perioperative complication was noticed. The specimen measured 22cm and 18cm in length respectively. Estimated blood loss was minimal in both cases. Oral diet was resumed on postoperative day 1. Patients were discharged on postoperative day 7 and day 6, respectively. At follow-up patients presented with an optimal cosmetic result without apparent scarring. Conclusions: For the first time a novel laparoscopic technique for sigmoid colon resection utilizing a single intraumbilical approach is presented. This new method allows further reduction of the surgical trauma and obviates any visible scar.

Ophthalmic Surg Lasers Imaging. 2009 May-Jun; 40(3): 245-50Kremer I, Ehrenberg M, Weinberger DBACKGROUND AND OBJECTIVE: When corneal perforation develops in patients with severe ocular surface disease and limbal stem cell deficiency following childhood trachoma infection, penetrating keratoplasty is doomed to fail. To overcome this problem, the use of a fresh-tissue corneolimbal covering graft is described. PATIENTS AND METHODS: Retrospective interventional case series of four patients who presented to a tertiary center from 2003 to 2005 with a large corneal perforation due to ocular surface disease. Emergency surgery consisted of suturing a fresh-tissue corneolimbal covering graft to the patients' peripheral sclera. RESULTS: The corneolimbal graft became partially incorporated into the perforated cornea, which healed by scar tissue, after a few months. The ocular epithelial surface improved considerably. There was no recurrence of corneal perforation during the follow-up period of 1 to 3 years. CONCLUSION: Fresh-tissue corneolimbal covering graft was found to be a useful technique for saving the integrity of the eye in cases of a large corneal perforation in patients with severe ocular surface disease, such as in childhood trachoma.

Laryngoscope. 2009 Jun 24; Mortensen M, Woo POBJECTIVES/HYPOTHESIS:: The microdebrider has become a valuable instrument for otolaryngologists. It is now used in the larynx for treatment of recurrent respiratory papillomatosis, laryngeal stenosis, and debridement of large cancers for airway control. There are few reported complications reported with the use of the microdebrider in the larynx. STUDY DESIGN:: A case report. METHODS:: A patient with a vocal fold polyp underwent removal of the polyp with a microdebrider at an outside institution. He presented to our clinic 2 months after the excision with a severely strained near aphonic voice. On rigid stroboscopic examination we saw a large anterior commisure laryngeal web with a granuloma. This was repaired by granuloma excision, web lysis, buccal graft, and laryngeal stent placement. CONCLUSIONS:: The microdebrider is an extremely valuable tool for the otolaryngologist. Violation of the epithelium and the lamina propria with muscle exposure can result in serious damage to the vocal folds. When using powered instrumentation the surgeon should use the upmost caution in the larynx to avoid causing debilitating injury and scar with subsequent dysphonia. Laryngoscope, 2009.

J Plast Reconstr Aesthet Surg. 2009 Jun 17; Schleich AR, Black DM, McCraw JB'No vertical scar' techniques of breast shaping have received increasing attention during the last decade and are sometimes viewed as 'new' methods. In this article, we provide a comprehensive introduction to the roots of this procedure. Raymond Passot has to be credited with the original design of 'no vertical scar' methods. We provide a contemporary translation of his original article written in French in 1925. The historical context of this new procedure was researched using original sources that were in French and German languages. The evolution of the procedure and its reception by Passot's contemporaries up to 1932 are examined, which give insight into the concepts of blood supply to the breast, shaping techniques and the aetiopathology of breast deformities in the pre-World War II era, which were successfully developed by the Austrian-German school of thought, resulting in the birth of modern breast shaping surgery based on Passot's 'no vertical scar' procedure. The lasting truths discovered in that era were frequently reinvented in the subsequent decades in English without crediting the original authors.

J Plast Reconstr Aesthet Surg. 2009 Jun 4; Brown BC, Moss TP, McGrouther DA, Bayat AGreater objective scar severity and visibility should intuitively cause greater psychosocial distress for patients. Previous research is contradictory and has employed non-validated scar severity measures whilst neglecting patient-rated severity. The aim of this study was to assess the effects of objective and patient-rated scar severity, scar type and location on psychosocial distress. Skin scars were quantitatively assessed on two independent occasions using the 'Manchester Scar Scale' (MSS) - a validated measure. Scars were scored twice independently. Patients also rated their scars (from 'very good' [zero] to 'poor' [four]) and good completed the Derriford Appearance Scale (DAS24) and Dermatology Life Quality Index (DLQI). Eighty-two patients, with an average+/-SD (range) age of 34+/-15 (16-65) years were recruited. Mean psychosocial questionnaire scores were: DAS24 45.5+/-17.8 (15-91); DLQI 7.5+/-6.7 (0-26). Participants had 1.9+/-1.5 (1-8) scars with an MSS score of 31.3+/-24.0 (6.6-162.0) and subjective score of 2.6+/-1.2 (0-4). Correlation between psychosocial distress and objective severity was not significant (DAS24 0.14 p=0.11; DLQI 0.16 p=0.06). Correlation between psychosocial distress and subjective severity was significant (DAS24 0.48 p

Rev Pneumol Clin. 2009 Jun; 65(3): 159-63Maalej S, Zidi A, Ayadi A, Chorfa A, Bourguiba M, Kilani T, Ben Kheder A, Drira IMediastinal fibrosis or fibrosing mediastinitis is a rare condition characterized by chronic fibrosis occurring in mediastinal structures, in proliferating fibrous scar tissue. The disease may be secondary or idiopathic. The authors report the case of a 46-year-old woman, without a particular past history, who, in December 2006, presented dyspnoea on exertion and a superior vena cava syndrome. Her chest X-ray showed a right laterotracheal opacity. Fiberoptic bronchoscopy revealed concentric tracheobronchial narrowing, severe hyperemia and mucosal edema. The chest computed tomography documented the obstruction of the superior vena cava, the right main bronchus and the right upper lobe bronchus secondary to a mediastinal mass. Mediastinoscopy revealed a hard and dense mass, surrounding the different structures of the mediastinum. Pathologic examination corroborated mediastinal fibrosis. No cause was determined. Prednisone and anticoagulant were prescribed during 2 years with a regression of dyspnoea and the superior vena cava syndrome and an important regression of radiological lesions. In conclusion, prolonged corticosteroids may be efficient in the treatment of idiopathic mediastinal fibrosis.

J Bone Joint Surg Br. 2009 Jun; 91(6): 725-9Livesey C, Wylde V, Descamps S, Estela CM, Bannister GC, Learmonth ID, Blom AWWe undertook a randomised controlled trial to compare the outcomes of skin adhesive and staples for skin closure in total hip replacement. The primary outcome was the cosmetic appearance of the scar at three months using a surgeon-rated visual analogue scale. In all, 90 patients were randomised to skin closure using either skin adhesive (n = 45) or staples (n = 45). Data on demographics, surgical details, infection and oozing were collected during the in-patient stay. Further data on complications, patient satisfaction and evaluation of cosmesis were collected at three-month follow-up, and a photograph of the scar was taken. An orthopaedic and a plastic surgeon independently evaluated the cosmetic appearance of the scars from the photographs. No significant difference was found between groups in the cosmetic appearance of scars at three months (p = 0.172), the occurrence of complications (p = 0.3), or patient satisfaction (p = 0.42). Staples were quicker and easier to use than skin adhesive and also less expensive. Skin adhesive and surgical staples are both effective skin closure methods in total hip replacement.

J Bodyw Mov Ther. 2009 Jul; 13(3): 262-7Valouchová P, Lewit KAmong the clinical symptoms caused by active scars in the abdominal region, back pain is very frequent. The muscles underneath such a scar appear to be less active on palpation than on the opposite side. To confirm this, 13 patients and 13 healthy controls were examined by surface electromyography (SEMG). We proceeded with SEMG of the straight abdominal muscles on both sides on lifting the head and the shoulders with the subject supine, and of the erector spinae with the patient prone. The patients with active scars were examined before and immediately after soft tissue treatment. SEMG examination showed increased muscle activity of the rectus abdominis in 6 cases on the side of the active scar and in 7 cases on the opposite side. This asymmetry decreased in 7 cases (p=0.045). Asymmetry was also found in the controls. This asymmetry was, however, significantly lesser than in the patients with an active scar (p=0.029). The discrepancy between palpatory and EMG findings is due to hypotony of the soft tissues on the side of the scar, giving the impression (illusion) that muscular activity is diminished on that side.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

J Hand Surg Am. 2009 Jun 17; Goldfarb CA, Monroe E, Steffen J, Manske PRPURPOSE: To evaluate the incidence and treatment of complications, suboptimal outcomes, and functional deficiencies after pollicization, and the need for additional surgical procedures. METHODS: A total of 73 index finger pollicizations performed by a single surgeon were identified. We retrospectively evaluated all available patient records for perioperative complications, suboptimal outcomes, and functional deficiencies of the pollicized digit. RESULTS: There were 8 complications in the perioperative period (including 3 cases of venous congestion, 4 cases of marginal necrosis, and 1 infection), requiring 12 surgical procedures; 1 pollicized digit was removed owing to nonviability. There were 8 suboptimal outcomes, including 7 cases of scar contracture and 1 with redundant skin, requiring 3 surgical procedures. Additional procedures related to functional deficiencies were performed in 26 total patients, 19 for poor opposition and 15 for limited extension. CONCLUSIONS: Most perioperative complications and suboptimal outcomes after pollicization are minor when an experienced surgeon is involved. Venous congestion, although uncommon, is a major viability risk and should be treated aggressively. In addition, a substantial number of pollicized digits have functional deficiencies related to anatomical limitations that can be addressed with muscle and tendon transfers. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Br J Ophthalmol. 2009 Jul; 93(7): 861-3Lee J, Winokur J, Hallak J, Azar DTAIM: To report a dovetail configuration for femtosecond-enabled penetrating keratoplasty (PK) with the corresponding laser parameters and suturing technique. METHODS: A 40-year-old man, with a history of penetrating corneal injury as a child, underwent femtosecond-enabled dovetail keratoplasty, anterior vitrectomy and secondary intraocular lens suturing to repair his corneal scar and aphakia. A partial thickness dovetail pattern was performed in the recipient cornea using the femotsecond laser. The posterior side-cut was initiated approximately 100 microm anterior to the Descemet membrane and extended obliquely towards the outer edge of a ring lamellar cut, positioned at approximately 300 microm stromal depth. The anterior side-cut was extended from the internal edge of the ring lamellar cut to the corneal surface. Using an artificial chamber, the femtosecond laser was used to create a full-thickness 0.2 mm oversized femtosecond-enabled dovetail trephination with similar anterior lamellar depth (approximately 300 microm). Wound closure, using interrupted 10-0 nylon sutures, was guided by preplaced radial alignment laser microincisions and tongue-in-groove midstromal suture positioning. RESULTS AND DISCUSSION: Excellent alignment and stability of the donor and recipient tissue were observed immediately postoperatively and 5 months after surgery. The feasibility of the "dovetail" pattern of PK and the tongue-in-groove suture positioning is demonstrated.

Dis Model Mech. 2009 Jul-Aug; 2(7-8): 344-58Boudoulas KD, Hatzopoulos AKAcute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal electromechanical continuum of the ventricular muscle and compromises its pumping capacity. Recent studies in animal models of ischemic cardiomyopathy suggest that transplantation of various stem cell preparations can improve heart recovery after injury. The first clinical trials in patients produced some encouraging results, showing modest benefits. Most of the positive effects are probably because of a favorable paracrine influence of stem cells on the disease microenvironment. Stem cell therapy attenuates inflammation, reduces apoptosis of surrounding cells, induces angiogenesis, and lessens the extent of fibrosis. However, little new heart tissue is formed. The current challenge is to find ways to improve the engraftment, long-term survival and appropriate differentiation of transplanted stem cells within the cardiovascular tissue. Hence, there has been a surge of interest in pluripotent stem cells with robust cardiogenic potential, as well as in the inherent repair and regenerative mechanisms of the heart. Recent discoveries on the biology of adult stem cells could have relevance for cardiac regeneration. Here, we discuss current developments in the field of cardiac repair and regeneration, and present our ideas about the future of stem cell therapy.

J Surg Res. 2009 May 3; Carter R, Sykes V, Lanning DINTRODUCTION: Apoptotic mechanisms are thought to be important in wound healing for the removal of inflammatory cells and evolution of granulation tissue. However, little is understood about the signal, propagation, and mechanisms responsible for triggering cell death in tissue injury, particularly during fetal wound repair. Understanding these signals may lead to insights regarding scarless wound healing. We hypothesized that differences in apoptosis would exist in mid- (E15) compared with late-gestational (E18) mice subjected to cutaneous wounds. We examined early apoptotic signals that may be initiated following tissue injury. METHODS: Pregnant, time-dated mice underwent laparotomy and hysterotomy on embryonic day 15 (E15) and 18 (E18). Full-thickness, excisional cutaneous wounds were made on the dorsum of the fetuses and dorsal skin harvested 15 and 45 min after wounding. Unwounded dorsal skin from additional fetuses collected at the same time points served as controls. The skin was processed to obtain protein, then levels of caspase 3, caspase 7, and poly ADP-ribose polymerase (PARP) were measured by Western blot. Cyclophilin levels were measured to ensure equal loading of protein. Histone-associated DNA complex formation was examined to provide further evidence of cellular apoptosis. RESULTS: There were no differences in total caspase 3 levels between E15 and E18 fetal tissue with or without wounding, nor was any cleavage of caspase 3 noted in any group. However, cleaved caspase 7 was present in the E15 skin with a >2-fold increase following wounding at both 15 and 45 min, yet absent in the E18 groups. Furthermore, levels of cleaved PARP were also increased by >2-fold at both 15 and 45 min in E15 wound groups, whereas a relatively small amount was only seen in the E18 wound groups at 45 min. DNA-histone fragmentation ELISA assay showed a 5-fold increase in the enrichment of histone-associated DNA fragments in the E15 wounded tissue compared with the time-matched controls at 45 min. This was not seen with the E18 tissue. CONCLUSIONS: Previously, we demonstrated that cutaneous wounds in E15 fetal mice heal in a scarless manner, while similar wounds in E18 mice heal with scar formation. Results from our current work demonstrate differences in apoptosis in mid- compared with late-gestational mouse skin as well as shortly after wounding. Our results suggest that in mid-gestational wounds, activation of apoptotic pathways may be mediated through effector caspase 7 signals with inactivation of PARP. This initiation of apoptotic signals following tissue injury may play a role in scarless wound repair.

Invest Ophthalmol Vis Sci. 2009 Jun 24; Feher J, Kovacs I, Pacella E, Keresz S, Spagnardi N, Balacco-Gabrieli CPurpose: To reveal the influence of retrobulbar capsaicin treatment on rats' eyes and to test protective effects of PEDF, a known neurotrophic and antiangiogenic substance on neurotrophic keratouveitis. Methods: A single retrobulbar injection of capsaicin (50 mg/kg ) was performed in young rats and the effect of 3.2 or 6.4 microg PEDF with retrobulbar administration was recorded. Tear fluid alterations were evaluated with Schirmer test, corneal alterations with slit lamp biomicroscopy. Histopathologic alterations were studied with light and electron microscopy. Number of leukocytes (myeloid cells) in the anterior and posterior chambers, peripheral retina and vitreous were quantitatively evaluated. Results: Reduced tear secretion was found in capsaicin treated rats as compared to control, but this effect was significantly attenuated by PEDF. Corneal ulceration developed and was followed by scar formation and neovascularisation in the capsaicin treated rats and it was also significantly attenuated with PEDF treatment. Leukocyte infiltration of the anterior and posterior chambers, as well as those of the peripheral retina and vitreous was also observed in capsaicin treated eyes, and was significantly reduced by PEDF treatment. Protective effects of PEDF were dose dependent for each parameters even if the treatment was initiated at the day 14 after capsaicin challenge. Conclusions: PEDF accelerated recovery of tear secretion, as well as prevented capsaicin-induced neurotrophic keratouveitis and peripheral vitreoretinal inflammation. These effects of PEDF described here for the first time, may have a clinical application in inflammatory and neovascular diseases of the eye.

J Gene Med. 2009 Jun 24; Pons J, Huang Y, Takagawa J, Arakawa-Hoyt J, Ye J, Grossman W, Kan YW, Su HBACKGROUND: Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner. METHODS: MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography. RESULTS: We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness. CONCLUSIONS: Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy. Copyright (c) 2009 John Wiley & Sons, Ltd.

Laryngorhinootologie. 2009 Jun 24; Bast F, Risteska K, Jovanovic S, Sedlmaier BTHE TOPICAL APPLICATION OF MITOMYCIN C IN THE TREATMENT OF SCAR FORMATION AND STENOSIS IN HOLLOW ORGANS OF THE HEAD AND NECK: A FIELD REPORTINTRODUCTION: The antibiotic und antitumoral effect of Mitomycin C (MMC), a derivative of STREPTOMYCES CAESPITOSUS, has been known since 1956. Besides its use as an adjunction in the treatment of breast, lung and prostate cancer, or as a second-line cytostatic drug for head and neck squamous cell carcinoma (HNSCC), since 1963, MMC has also been successfully used in the suppression of post-operative scar formation, particularly in the field of ophthalmology. This is due to its modulation of fibroblast activity, which enables decreased scarring and fibrosis. In this résumé, we wish to recapitulate our long years of experience in the topical application of Mitomycin C in the treatment of scar formation and stenosis in head and neck organs. PATIENTS AND METHODS: A retrospective analysis on the basis of clinical disease courses and findings (image documentation, questionnaires, pulmonary function tests) covering an examination period of 10 years, was performed on 40 patients with stenosising lesions and a mean age of 54 years. The fields of application included laryngeal, tracheal, oesophageal stenosis and stenosis of the external ear canal and the choane. RESULTS: After combined application of MMC and surgical intervention in cases of recurrent stenosising processes in head and neck organs, especially the larynx and the trachea, a sustained improvement was achieved in the pre-operative stenosis level as well as in the pre-operative, severely limited, forced inspiratory volume in 1 second (F1V1). CONCLUSION: The topical application of MMC appears to be an effective adjunction as a concept of treatment for stenosising, scar-forming lesions. This topical application, however, is not a substitute for correct diagnosis and appropriate surgical treatment. It must be regarded as a purely adjunctive manoeuvre. During the 10 years in which it was used, the clinical findings confirmed an enhancement in the containment of complex cases without the occurrence of any complications.

Med Hypotheses. 2009 Jun 18; Schwartsburd PMTissues adjacent to invasive cancers are characterized by wound non-healing, although wounds in normal tissues heal perfectly with the formation of a scar. Cancer-related disorders responsible for wound non-healing have serious clinical impacts, among which are restrictions for the cancer removal via surgical operation. It is not clear how a cancer is capable of deregulating the program of wound healing in normal differentiated tissues adjacent to the cancer. There is good reason to believe that, in cancers (as in fetal-like tissues), there operates a scar-free healing program similar to embryonic healing, whereas in adult tissues a scar-forming healing program of wound repair acts. It can be expected that competitive interactions between these two opposite programs will disrupt the normal development of the scar-forming healing program in normal tissues adjacent to cancer (NTAC). The aim of the present study was to check this hypothesis by comparing the differences and similarities at different stages of embryonic scar-free wound healing, adult/mature scar-forming wound healing, and cancer-induced non-healing observed in NTAC wounds. The identification of certain principal distinctions in features and key regulators between the programs acting in these types of wound repair can be useful for scar-improving wound repair.

Vet Surg. 2009 Jun; 38(4): 439-44Olivieri M, Voghera SG, Fossum TWObjectives- To evaluate the clinical outcome of left partial arytenoidectomy by video-assisted laser diode photoablation as a surgical treatment for canine laryngeal paralysis (LP). Study Design- Case series. Animals- Dogs with bilateral LP (n=20). Methods- After endoscopic diagnosis of bilateral LP, left partial arytenoidectomy was performed by photoablation of arytenoid cartilage tissue using a diode laser (600 mum diameter, 15 W power, 980 nm wave length) to increase the width of the rima glottidis. Outcome was evaluated endoscopically (1 and 6 months) and clinically (1, 6, and 12 months). Results- No substantial complications occurred during photoablation or in the immediate postoperative period. Postoperative width of the rima glottidis ranged from 6 to 10 mm at its widest aspect. At 1 month, respiratory function after walking and short running appeared good. Clinical and endoscopic examination revealed good outcome at 1 and 6 months. At 6 months, there was no evidence of hypertrophic scar, hypertrophic granulation tissue, or stricture of the laryngeal glottis in any dog. Two dogs developed aspiration pneumonia after 12 months. Conclusions- Partial arytenoidectomy using video-assisted diode laser photoablation appears to be an effective technique for treating LP. Clinical Relevance- Partial arytenoidectomy by diode laser photoablation should be considered as an alternative technique for treatment of canine LP.

Dermatol Surg. 2009 Jun 22; McGuire CS, Gladstone HBBACKGROUND The upper third of the face is integral to our perception of youth and beauty. While the eyelids anchor this facial cosmetic unit, the eyebrows and forehead are intrinsically linked to the upper eyelids, and their position and texture play an important role in creating pleasing eyes as well as conveying mood and youth. The most common browlifts are performed with endoscopic visualization. Yet, this technique requires special equipment and a prolonged learning curve. OBJECTIVE To demonstrate a novel pretrichial technique and to review different browlift methods and their potential adverse effects. METHODS Case series and review of the literature. RESULTS The pretrichial browlift results in a mild to moderate browlift with secondary smoothing of the forehead topography. Aside from bruising and swelling, it results in minimal adverse effects. Other techniques are also effective but may create a larger scar such as a direct browlift, may be more difficult in terms of approach such as the browpexy, or require endoscopes. CONCLUSION Browlifts are an important procedure in rejuvenating the upper third of the face and improving the overall facial aesthetic appearance. The pretrichial browlift is a less invasive open technique that is safe and effective for the appropriate patient. The authors have indicated no significant interests with commercial supporters.

BJU Int. 2009 Jun 22; Naselli A, Introini C, Bertolotto F, Spina B, Puppo POBJECTIVE To determine if narrow-band imaging (NBI) can be used to detect high-grade cancerous lesions missed with the white light at the time of a second transurethral resection (TUR) of high-grade non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS Consecutive patients with newly diagnosed high-grade NMIBC were enrolled in a prospective observational study. Patients with incomplete resection or absence of muscle tissue in the specimen were excluded. About 1 month after the first TUR, NBI cold-cup biopsies were taken from areas suspicious for urothelial cancer at the end of an extensive white-light second TUR protocol including: (i) resection of the scar of the primary tumour; (ii) resection of any overt or suspected urothelial lesions; and (iii) six random cold-cup biopsies of healthy mucosa. RESULTS In 2008, 47 consecutive patients were recruited after giving written consent (median age 62 years, range 49-83, 39 men and eight women). Nine patients (19%) had macroscopic or microscopic high-grade NMI urothelial cancer, whereas one was reassessed as having muscle-invasive disease at the white-light second TUR plus the six random biopsies. NBI biopsies were taken in 40 of the 47 patients and detected six more patients with high-grade cancerous tissue (13%). In all 16 of the 47 patients (34%) were found to have residual/recurrent cancer using our extensive protocol of second TUR followed by NBI biopsies. CONCLUSIONS Adding NBI biopsies at the end of an extensive second TUR protocol in patients with newly diagnosed high-grade NMIBC can lead to the identification of patients with otherwise missed high-grade residual/recurrent urothelial carcinoma.

J Plast Reconstr Aesthet Surg. 2009 Jun 17; Liu Y, Song B, Jin J, Zhu S, Pan LWe present a patient with a neck burn scar contracture. A parascapular free flap is used to re-surface the cervical defect, while the resultant donor-site defect is reconstructed by a freestyle pedicled thoracodorsal artery perforator flap. With the introduction of a freestyle pedicled perforator flap, large-sized donor-site defects of the parascapular flap can be closed easily and safely with minimal donor-site morbidity. The parascapular flap is the workhorse flap for defect reconstruction in our centre. The advantages of this flap have been well documented in the literature. One of the main drawbacks of the parascapular flap is that the donor site is difficult to close primarily if the flap width is significantly wide. Although Nassif(1) reported that it can be closed directly even if the flap width is up to 15cm, in our experience, it is possible and easy to close the donor site directly when the flap width is under 12cm. Alternatively, split-thickness skin grafting is needed to prevent the wound dehiscence. In this article, we describe a technique in which the donor site of the parascapular flap was reconstructed by a freestyle pedicled thoracodorsal artery perforator flap, thereby reducing the donor-site morbidity to the minimum.

Stem Cells. 2009 Apr 9; Du Y, Carlson EC, Funderburgh ML, Birk DE, Pearlman E, Guo N, Kao WW, Funderburgh JLCorneal scarring from trauma and inflammation disrupts vision for millions worldwide, but corneal transplantation, the primary therapy for corneal blindness, is unavailable to many affected individuals. In this study, stem cells isolated from adult human corneal stroma were examined for the ability to correct stromal opacity in a murine model by direct injection of cells into the corneal stroma. In wild type mice, injected human stem cells remained viable for months without fusing with host cells or eliciting immune T-cell response. Human corneal-specific extracellular matrix, including the proteoglycans lumican and keratocan, accumulated in the treated corneas. Lumican null mice have corneal opacity similar to that of scar tissue as a result of disruption of stromal collagen organization. After injection with human stromal stem cells, stromal thickness and collagen fibril defects in these mice were restored to that of normal mice. Corneal transparency in the treated mice was indistinguishable from that of wild-type mice. These results support the immune-privilege of adult stem cells and the ability of stem cell therapy to regenerate tissue in a manner analogous to organogenesis and clearly different from that of normal wound healing. The results suggest that cell-based therapy can be an effective approach to treatment of human corneal blindness.

J Craniomaxillofac Surg. 2009 Jun 18; Tan OBACKGROUND AND OBJECTIVE: The classic forehead flaps, which are designed vertically, two-staged and exteriorised pedicled peninsular flaps, are still a reconstructive option for nasal and periorbital defects. However, some drawbacks such as conspicuous donor-site scar, multi-staged procedure, rather short pedicle, hairy appearance (in narrow foreheads), and inability to use the forehead flap when the donor site is involved are often encountered during surgery. To avoid these issues, three unusual designs of the forehead flap are presented, and also a new algorithm is proposed to guide surgeons in their solutions. MATERIALS AND METHODS: Nineteen patients (10 women and nine men) were managed with 21 forehead flaps to restore the nasal, medial canthal and frontal defects caused by skin tumours. The flaps were applied as interpolation island, V-Y island, and transverse peninsular designs in 12, four and three patients, respectively. All donor sites were closed primarily except one, where a split thickness skin graft was used. RESULTS: The average follow-up was 14 months. All flaps survived (totally) but in one partial necrosis developed. Aesthetic and functional recoveries were acceptable in all patients. CONCLUSIONS: Based on the algorithm presented, the forehead flaps with their superb anatomic characteristics including rich vascular supply and pliable skin can be safely used in either classic or extraordinary fashion for small to medium sized defects of the nasoorbital and frontal regions.

Heart. 2009 Jun 18; Puranik R, Tsang V, Broadley A, Nordmeyer J, Lurz P, Muthialu N, Graham D, Walker F, Cullen S, de Leval M, Bonhoeffer P, Taylor A, Muthurangu VOBJECTIVE: To assess autograft, homograft and ventricular function, as well as exercise capacity, in adult patients who have undergone the Ross procedure. SETTING: Single centre paediatric and adult congenital heart disease unit. PATIENTS: 45 subjects (24.6y, range 16.9-52.2y) who underwent the Ross procedure between 1994 and 2006 (8.1y post Ross operation, range 2.0-14.0y). INTERVENTIONS: Cardiovascular magnetic resonance imaging, echocardiography and cardiopulmonary exercise testing. MAIN OUTCOME MEASURES: Autograft and homograft stenosis, and regurgitation. Autograft size. Bi-ventricular function, scar volume and exercise capacity. RESULTS: Mean autograft regurgitation was 6.8+/-8.3% (trivial regurgitation) and diameter was 40.0+/-7.0mm. Mean homograft velocity was 2.4+/-0.6m/s (mild-moderate stenosis) and regurgitation was 6.1+/-8.3% (trivial regurgitation). Biventricular systolic function was normal (LV EF 63.1+/- 6.4% and RV EF 60.1+/- 7.6%). In 38% of cases there was evidence of LV scar, mostly noted within the inter-ventricular septum. The mean exercise capacity achieved was 87+/- 22% of predicted. There was no correlation between exercise capacity and ventricular function or scar. CONCLUSION: This study demonstrates minor autograft and homograft dysfunction in the majority of patients post Ross procedure, associated with good ventricular function and exercise capacity. In addition, minor scar was present in a third of patients with no functional consequences.

J Ethnopharmacol. 2009 Jun 15; Deshmukh PT, Fernandes J, Atul A, Toppo EETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantea R.Br. (Asclepiadaceae) is a perennial undershrub found chiefly in wastelands throughout India. It has been reported as a traditional folkloric medicine for a variety of alignments. The plant Calotropis gigantea is also used in some parts of India for wound healing in combination with other plants. However there are no scientific reports on wound healing activity of the plant Calotropis gigantea R.Br. AIM OF THE STUDY: To investigate the effects of Calotropis gigantea root bark on wound healing activity in rats by excision, incision and dead space wound healing models in rats. METHODOLOGY: Wistar albino rats of either sex weighing between 180-200g of either sex were topically treated with extract formulated in ointment by using simple ointment BP as base. 5 % (w/w) ointment once daily in excision wound model. Calotropis gigantea ethanolic extract were given orally at a dose of 100mg/kg, 200mg/kg, and 400mg/kg in incision and dead space wound healing models. Rats of standard groups were treated with 5% Povidone iodine ointment topically. The percentage wound closure; epithelization time, Hydroxyproline content and scar area on complete epithelization were measured. RESULTS: Topical application of Calotropis gigantea in excision wound model increased the percentage of wound contraction. Scar area and epithelization time was decreased. In incision wound and dead space wound breaking strength of wounds and hydroxyproline was increased. CONCLUSION: Calotropis gigantea accelerated wound healing in rats and thus supports its traditional use.

Ann Plast Surg. 2009 Jul; 63(1): 15-20Bruekers SE, van der Lei B, Tan TL, Luijendijk RW, Stevens HPMany techniques have been described for umbilicoplasty after abdominoplasty, but none of these techniques seems ideal. In this report, we wish to report a new "scarless" umbilicoplasty technique, which bears many of the characteristics of an ideal technique: it is easy to perform and results in the complete absence of visible scars and with a preferred vertical orientation. The aesthetic results of this technique are subjectively and objectively evaluated as compared with the classic umbilicoplasty and these results are discussed among the English language literature.In the period of 2004 to 2005, a series of 138 female patients have had an abdominoplasty with either the classic umbilicoplasty (n = 31) or with our scarless umbilicoplasty (n = 107). After a follow-up period of at least 3 (of 6) months, a questionnaire was send to all of these patients to evaluate patient satisfaction. Twenty-five patients from the classic umbilicoplasty group responded, 53 patients from the scarless umbilicoplasty group. Age (mean 45 with range, 22-66 years) and body mass index (29 with range, 22-35) did not differ among both groups. Also a random selection of fifteen photos from both groups was analyzed and rated according to the system of Strasser by an independent panel.There were no major complications in both groups, but in the classic group, there were some cases with hypertrophic scarring. Patients who underwent the scarless umbilicoplasty technique graded the appearance of their umbilicus significantly better on shape, depth, hygiene, and scar. No significant differences were found in grading size and wound healing. Objective evaluation of the photos demonstrated significant better results for the scarless umbilicoplasty technique.Based on our subjective and objective analysis we conclude that our new technique of the scarless umbilicoplasty features many of the characteristics of the ideal umbilicoplasty: a rather simple and reliable method for creating a natural looking umbilicus when performing an abdominoplasty.

Ophthalmic Res. 2009 Jun 18; 42(2): 90-95Hashemian MN, Moghimi S, Kiumehr S, Riazi M, Amoli FABackground: To evaluate and compare the effect of different doses of subconjunctival bevacizumab with betamethasone on the development of corneal major new vessels in a rat model of corneal chemical injury. Methods: The right eyes of 100 male Sprague-Dawley rats were randomly divided into 10 experimental groups (n = 10 per group). Chemical cauterization of the cornea was performed by using silver nitrate/potassium nitrate sticks. Immediately following corneal cauterization, the animals in groups 1-5 received subconjunctival injections of 0.02 ml of normal saline (control A), betamethasone LA (6 mg/ml) and different doses of bevacizumab (1, 5 and 25 mg/ml), respectively. In another experiment, the animals in groups 6-10 received subconjunctival injections of 0.02 ml of normal saline (control B), betamethasone LA (6 mg/ml) and different doses of bevacizumab (1, 5 and 25 mg/ml), respectively, 7 days following corneal cauterization. The numbers of major thick-walled vessels originating from the limbus reaching the corneal scar were counted 7 days after corneal cauterization in groups 1-5 and 14 days after corneal cauterization in groups 6-10. Results: The number of major vessels in groups 1-5 was 19.63 +/- 3.77, 17.25 +/- 5.33, 16.10 +/- 5.02, 12.89 +/- 2.70 and 12.36 +/- 4.45 when assessed 7 days after corneal cauterization, respectively. Administration of betamethasone in group 2 had no significant effect on the corneal major vessel count compared to control A. The number of major vessels in groups 4 and 5 (bevacizumab 5 and 25 mg/ml) was significantly lower than that of group 1 (p < 0.01, Student's t test). The number of vessels in groups 6-10 was 12.55 +/- 5.64, 11.30 +/- 9.33, 5.50 +/- 6.34, 2.73 +/- 4.73 and 2.67 +/- 3.77 when assessed 14 days after corneal cauterization, respectively. Subconjunctival administration of betamethasone 7 days after corneal cauterization did not reduce the amount of corneal major vessels compared to control B. Administration of 0.02 ml of bevacizumab in doses of 1, 5 and 25 mg/ml 7 days after corneal cauterization significantly reduced the amount of major vessels compared to group 6 (p = 0.01, p < 0.01 and p < 0.01, respectively). There was no significant difference in percent area of corneal scar between different groups. Conclusion: Single subconjunctival injection of bevacizumab is efficacious in the prevention of formation as well as regression of major vessels compared to betamethasone in this rat model of corneal neovascularization. Even lower doses of bevacizumab might be efficacious.

Int Wound J. 2009 Jun; 6(3): 214-24El Kahi CG, Atiyeh BS, Abdallah Hajj Hussein I, Jurjus R, Dibo SA, Jurjus A, Jurjus AThe myofibroblast, a major component of granulation tissue, is a key cell during wound healing, tissue repair and connective tissue remodelling. Persistence of myofibroblasts within a fibrotic lesion leads to excessive scarring impairing function and aesthetics. Various wound-healing cytokines can be modulated by topical application of active agents to promote optimal wound healing and improve scar quality. Thus, the myofibroblast may represent an important target for wound-healing modulation to improve the evolution of conditions such as hypertrophic scars. The purpose of this work is to study the modulation of myofibroblasts and integrin alphavbeta3 in a full thickness wound performed on rabbits treated with different topical agents using: (1) saline, (2) Tegaderm occlusive dressing (3) silver sulfadiazine and (4) moist exposed burn ointment (MEBO). The reepithelialisation was 4 days faster in the MEBO group compared with the other therapies with less oedema formation, delayed contraction, less inflammatory cells and the lowest transepidermal water loss (TEWL) resulting in a soft scar. Although alpha-smooth muscle actin (alpha-SMA) was the highest around day 12 in the MEBO group, wound contraction and myofibroblast's activity were the least for the same period probably because of a downregulation of the integrin alphavbeta3. It seems that the effect of MEBO could be more pronounced on force transmission rather then on force generation. Greater insight into the pathology of scars may translate into non surgical treatments in the future and further work in myofibroblast biology will eventually result in efficient pharmacological tools, improving the evolution of healing and scar formation.

J Appl Physiol. 2009 Jun 18; Eliasson P, Andersson T, Aspenberg PInjured tendons require mechanical tension for optimal healing, but it is unclear which genes are upregulated and responsible for this response. We unloaded one Achilles tendon in rats by Botox injections in the calf muscles. The tendon was then transected and left to heal. We studied mechanical properties of the tendon callus, as well as mRNA expression, and compared them too loaded controls. Tendon calluses were studied 3, 8, 14 and 21 days after transection. Intact tendons were studied similarly for comparison. Altogether 110 rats were used. The genes were chosen for proteins marking inflammation, growth, extracellular matrix and tendon specificity. In intact tendons, procollagen III and tenascin-C were more expressed in loaded than unloaded tendons, but none of the other genes was affected. In healing tendons, loading status had small effects on the selected genes. However, TNF, TGF-b1 and procollagens I and III were less expressed in loaded callus tissue day 3. At day 8, also procollagens I and III, LOX and scleraxis had a lower expression in loaded calluses. However, by day 14 and 21, procollagen I, COMP, tenascin-C, tenomodulin and scleraxis were all more expressed in loaded calluses. In healing tendons, the transverse area was larger in loaded samples, but material properties were unaffected, or even impaired. Thus, mechanical loading is important for growth of the callus, but not its mechanical quality. The main effect of loading during healing might thereby be sought among growth stimulators. In the late phase of healing, tendon-specific genes (scleraxis and tenomodulin) were upregulated with loading, and the healing tissue might to some extent represent a regenerate rather than a scar. Key words: Unloading, tendon healing, inflammation, extracellular matrix, mechanobiology.

Spine J. 2009 Jun 17; Kim DH, Rhim R, Li L, Martha J, Swaim B, Banco RJ, Jenis LG, Tromanhauser SGBACKGROUND CONTEXT: Morbidity associated with autologous bone graft harvest is an important factor in determining the utility of expensive alternatives such as recombinant bone morphogenic protein. The most frequently reported complication associated with graft harvest is chronic pain. PURPOSE: To prospectively determine the degree of pain and morbidity associated with autologous iliac crest bone graft harvest and its effect on activities of daily living. STUDY DESIGN: Prospective observational cohort study. PATIENT SAMPLE: One hundred ten adult patients undergoing elective posterior lumbar spinal fusion surgery involving autologous iliac crest bone graft harvest. OUTCOME MEASURES: Patient self-reported Visual Analog Scale (VAS) scores for pain and a study-specific questionnaire regarding activities of daily living. METHODS: One hundred ten patients were prospectively enrolled. Postoperative VAS scores (0-100) for harvest site pain were obtained at 6-week, 6- and 12-month follow-up. Patients completed a 12-month questionnaire regarding the persistence of specific symptoms and resulting limitation of specific activities. RESULTS: One hundred four patients were available for 1-year follow-up. Mean VAS pain scores (scale 0-100) at 6 weeks, 6 and 12 months were 22.7 (standard deviation [SD], 25.9), 15.9 (SD, 21.5), and 16.1 (SD, 24.6), respectively. At 12 months, 16.5% reported more severe pain from the harvest site than the primary surgical site, 29.1% reported numbness, and 11.3% found the degree of numbness bothersome, whereas 3.9% were bothered by scar appearance. With respect to activity limitations resulting from harvest site pain at 1 year, 15.1% reported some difficulty walking, 5.2% with employment, 12.9% with recreation, 14.1% with household chores, 7.6% with sexual activity, and 5.9% irritation from clothing. CONCLUSIONS: There is a significant rate of persistent pain and morbidity from iliac crest bone graft harvest when associated with elective spine surgery. Mean pain scores progressively decline over the first postoperative year. Nevertheless, harvest site pain remains functionally limiting in a significant percentage of patients 1 year after surgery. Rates of functional limitation are higher than previously reported and may be because of increased sensitivity of the prospective study design and targeted investigation of these specific symptoms. Validity of these findings is necessarily limited by patient ability to discriminate harvest site pain from alternative sources of back and buttock pain.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Klin Onkol. 2009; 22(1): 17-21Bustová IBACKGROUND: Locally advanced breast carcinoma represents a disease, where the combination of treatment--chemotherapy with antracycline and radiotherapy--is generally accepted as standard therapy. This management can be limited by cardiotoxicity. Cardiotoxicity is a rare complication of breast cancer treatment and the incidence and severity of cardiotoxicity are dependent on cumulative dose of antracyline, the type and combination of drugs used, the presence of coexsistin diseases (cardiac diseases, diabetes mellitus), risk faktors and use, the way of radiotherapy and combination therapy in the treatment of locally advanced breast carcinoma. MATERIAL AND METHODS: 64 patients (average age 57) with locally advanced breast carcinoma stage III were treated chemotherapy FAC. The chemotherapy consisted of doxorubicin 50 mg/m2, i.v. infusion day 1, cyclophosphamid 500 mg/m2, day 1 a 5-flourouracil 500 mg/m2 - day 1 and day 8. Every 21 days, sequential surgery of breast carcinoma, adjuvant chemotherapy FAC and irradiation. Patients had 6 cycles of chemoterapy. Cumulative doxorubicine dose was 300-350 mg/m2, radiotherapy was undertaken in all cases. It was administered after chemotherapy and was planned according to the well-established technigue. It included the chest wall and regional lymph nodes after mastectomy and breast with scar and regional lymph nodes after parcial mastectomy. The condition of the heart was studied using echocardiography which were performed before start of chemotherapy FAC and during of chemotherapy after 1 year of beginning of combination treatment chemotherapy FAC and radiotherapy after 2, 3, 4, 5 and more years. RESULTS: Occurrence of cardiotoxicity during 6 cycles of (neoadjuvant and adjutant) chemotherapy FAC was monitored by LVEF. Cardiotoxicity was find out at 9 patients from 64 patients of the group (14%)-toxicity grade (G) 1 and G2. After combination treatment neoadjuvant and adjuvant chemotherapy FAC and radiotherapy was found out at 9 patients from 63 patients of the group (14.3%)-cardiotoxity G1. Cardiotoxicity after combination of chemotherapy FAC and radiotherapy after 2 years was found out at 6 patients (9.7%) G1 and cardiotoxicity after combined treatment of chemotherapy FAC and radiotherapy was found out after 3, 4, 5, and more years--at 3 patients (5.9%)--cardiotoxicity G1. Incidence of clinical cardiac failure was 4.7%--1 patient died of cardiac failure and 2 patients died of heart attack. CONCLUSIONS: The incidence of the risk of cardiotoxicity is rare event but the risk of damage to the cardiovascular system following radiotherapy and antracyclines exists, although cardiotoxic effects of both these drugs groups have been well known. The cardiotoxicity apperas in the process of the chemotherapy with doxorubicine, in combination of the chemotherapy with doxorubicine and radiotherapy, but also in longer time intervals from the beginning of the treatment (2, 3, 4, 5 and more years).

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Arch Dermatol Res. 2009 May 23; 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) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Semin Immunopathol. 2009 Jun 17; Zhou P, Wirthlin L, McGee J, Annett G, Nolta JImmune-deficient mouse models of liver damage allow examination of human stem cell migration to sites of damage and subsequent contribution to repair and survival. In our studies, in the absence of a selective advantage, transplanted human stem cells from adult sources did not robustly become hepatocytes, although some level of fusion or hepatic differentiation was documented. However, injected stem cells did home to the injured liver tissue and release paracrine factors that hastened endogenous repair and enhanced survival. There were significantly higher levels of survival in mice with a toxic liver insult that had been transplanted with human stem cells but not in those transplanted with committed progenitors. Transplantation of autologous adult stem cells without conditioning is a relatively safe therapy. Adult stem cells are known to secrete bioactive factors that suppress the local immune system, inhibit fibrosis (scar formation) and apoptosis, enhance angiogenesis, and stimulate recruitment, retention, mitosis, and differentiation of tissue-residing stem cells. These paracrine effects are distinct from the direct differentiation of stem cells to repair tissue. In patients at high risk while waiting for a liver transplant, autologous stem cell therapy could be considered, as it could delay the decline in liver function.

Endoscopy. 2009 Jun; 41(6): 498-503Kunisaki C, Takahashi M, Nagahori Y, Fukushima T, Makino H, Takagawa R, Kosaka T, Ono HA, Akiyama H, Moriwaki Y, Nakano ABACKGROUND: We retrospectively evaluated the predictive factors for lymph node metastasis in poorly differentiated early gastric cancer (poorly differentiated tubular adenocarcinoma, signet-ring cell carcinoma, mucinous adenocarcinoma) in order to examine the possibility of endoscopic resection for poorly differentiated early gastric cancer. METHODS: A total of 573 patients with histologically poorly differentiated type early gastric cancer (269 mucosal and 304 submucosal), who had undergone curative gastrectomy, were enrolled in this study. Risk factors for lymph node metastasis were evaluated by univariate and logistic regression analysis. RESULTS: Lymph node metastasis was observed in 74 patients (12.9%) (6 with mucosal cancer and 68 with submucosal cancer). By univariate analysis risk factors for lymph node metastasis were lymphovascular invasion (LVI) (presence), depth of invasion (submucosa), and tumor diameter (> 20 mm), ulcer or ulcer scar (presence), and histological type (mucinous adenocarcinoma). By multivariate analysis, risk factors for lymph node metastasis were LVI, depth of invasion, and tumor diameter. In mucosal cancers, the incidence of lymph node metastasis was 0% irrespective of LVI in tumors smaller than 20 mm, and 1.7% in tumors 20 mm or larger without LVI. In submucosal cancers, the incidence of lymph node metastasis was 2.4% in tumors smaller than 20 mm without LVI. CONCLUSIONS: A histologically poorly differentiated type mucosal gastric cancer measuring less than 20 mm and without LVI may be a candidate for endoscopic resection. This result should be confirmed in a larger study with many patients.

Curr Drug Discov Technol. 2009 Jun; 6(2): 82-90Ibarra A, Martiñón SSpinal cord (SC) injury causes serious neurological alterations that importantly disturb the physical, emotional and economical stability of affected individuals. Damage to the neural tissue is primarily caused by the lesion itself and secondarily by a multitude of destructive mechanisms that develop afterwards. Unfortunately, the restoring capacity of the central nervous system is very limited because of reduced intrinsic growth capacity and non-permissive environment for axonal elongation. The regenerative processes are blocked by diverse factors such as growth inhibitory proteins and the glial scar formed in the site of lesion. In spite of these problems, central neurons regenerate if a permissive environment is provided. In line with this thought, some pharmacological compounds have been tested to achieve neuroregeneration. The main objective of this manuscript is to provide the state-of-art of chemotherapeutic treatments for spinal cord regeneration after injury in the field. The efficacy and usefulness of different therapeutic strategies will be reviewed, including Rho-ROCK inhibitors, cyclic AMP-enhancers, glial scar inhibitors and immunophilin ligands. Aside from this, the use of hydrogels alone or in combination with drugs, growth factors or stem cells will also be revised.

Injury. 2009 Jun 12; Ahmadabadi MN, Karkhaneh R, Roohipoor R, Tabatabai A, Alimardani APURPOSE: To report the clinical presentation, treatment approach and natural course of a series of chorioretinitis sclopetaria patients. METHODS: Thirteen consecutive patients with clinical diagnosis of chorioretinitis sclopetaria were included in a case series study during 2000-2006. All patients underwent clinical examination, including the best-corrected Snellen visual acuity, slit-lamp examination, applanation tonometry, funduscopy and fundus photography. Three-port standard vitrectomy was performed in two patients due to dense vitreous haemorrhage and suspected retinal detachment in both cases. All patients were followed up at week 4, months 2 and 6 and then every 6 months. RESULTS: The mean age of the patients was 16+/-6 (range: 5-27) years and 11 patients (84.6%) were male. The mean follow-up period was 37+/-18 (range: 17-82) months. Baseline best-corrected visual acuity ranged from no light perception (NLP) to 20/1600, and final visual acuity range was from NLP to 20/1200. Only one patient developed acute retinal detachment, and the retina remained attached in others through follow-up. CONCLUSION: In spite of severe retinal and choroidal injuries in chorioretinitis sclopetaria, retinal detachment does not usually occur, probably due to spontaneous retinopexy and scar formation. Whilst dealing with chorioretinitis sclopetaria, it is important to make an accurate diagnosis to prevent unwarranted surgical intervention.

Wound Repair Regen. 2009 Jun 12; Lee WR, Park JH, Kim KH, Kim SJ, Park DH, Chae MH, Suh SH, Jeong SW, Park KKWound healing is a dynamic and complex process of tissue repair that involves a number of cellular and molecular events. It proceeds from inflammatory response to reepithelialization and finally to formation of a permanent scar. Alginate is a polymer of guluronic and mannuronic acid that is used as a scaffolding material in biomedical applications. For the purpose of studying wound healing, full-thickness skin defects were produced on the dorsal area in rats. We measured the relative sizes of the wounds on days 3, 5, 7, 14, and 28. The wound sizes were decreased in the alginate-treated group compared with the control group and the vaseline-treated group. The expressions of transforming growth factor-beta1, fibronectin, and vascular endothelial growth factor were significantly decreased in the alginate-treated group compared with the control group, while the expression of collagen-I was increased in the alginate-treated group, as indicated by Western blotting and immunohistochemical staining. These data suggest that alginate has significant wound healing promoting activity. The results from the present study indicate that the effect of alginate on wound healing may involve biological mechanisms associated with the expression of transforming growth factor-beta1, fibronectin, vascular endothelial growth factor, and collagen-I.

Am J Clin Oncol. 2009 Jun 12; Newlin HE, Indelicato DJ, Abbitt P, Marshall J, Wymer D, Grobmeyer S, Haigh L, Copeland E, Morris CG, Mendenhall NPPURPOSE:: Scarring in the tumor bed may mask or mimic local recurrence of tumor on surveillance mammography. Type of surgical closure technique used during lumpectomy may impact the pattern or density of scar tissue apparent in the tumor bed on mammography. This study sought to determine whether surgical closure type affects tumor-bed scar formation and impacts interpretation of surveillance mammography in women treated with breast-conserving therapy for early-stage breast cancer. MATERIALS AND METHODS:: One hundred women who received breast-conserving therapy were selected; 99 of them had 2-year post-treatment mammograms for the treated breast. Craniocaudal and mediolateral oblique views were reviewed by 3 subspecialty radiologists who routinely read mammograms. The mammograms were scored on 5-point scales for overall breast density and scarring within the tumor bed. RESULTS:: The analyses did not demonstrate greater scarring or density in breast status post superficial closure compared with breast status post full-thickness closure, or vice versa (P > 0.05 for scarring and density). There were no detectable differences between the 2 closure techniques either within the data from individual reviewers, within the composite data for the entire group of reviewers, or in instances where 2 of 3 reviewers agreed (P > 0.05). There was significant interobserver variability in scoring among the mammographers for both scarring (P = 0.001) and density (P < 0.0001). CONCLUSION:: Based on our study of the 2-year post-treatment mammograms, there was no evidence that closure technique impacts degree of scarring in the tumor bed. However, striking interobserver variability in scoring density and scarring was noted.

G Ital Dermatol Venereol. 2009 Jun; 144(3): 243-57Viera MH, Amini S, Konda S, Barman BKeloids and other scars are different manifestations of the normal wound healing process. If located in visible areas, scars may have a psychological impact that could affect the quality of life of the scar-bearing population. Good preoperatory planning including hiding incisions in natural anatomical landmarks or placing them parallel to relaxed skin tension lines are among the techniques used to improve the cosmesis of scars. Once a prominent or noticeable scar has developed, multiple therapeutic modalities can be applied including surgical excision, although high recurrence rates precludes its use as monotherapy. Several advanced surgical correction techniques including Z-plasty and W-plasty may be useful in repositioning scars. Other modalities that have been reported to improve scar cosmesis include cryosurgery, radiotherapy, lasers, and skin substitute grafts. Adjuvant postsurgical treatment modalities have reduced dramatically the recurrence rates associated with the removal of the scar. In this review of the literature the authors discuss evidence based data related to the abovementioned modalities and other topical and intralesional therapies including occlusion, compression, silicone, corticosteroids, interferons, imiquimod, resiquimod, tacrolimus, 5-fluorouracil, retinoids, as well as the role of several over-the-counter agents such as onion extract, vitamin E and the combination of hydrocortisone, vitamin E and silicone. Finally, they address newer modalities including vascular endothelial growth factor inhibitor, transforming growth factor-3, interleukin-10, mannose-6-phosphate, UVA-1, narrowband UVB, intense pulsed light and photodynamic therapy. Ultimately, the decision of choosing the most appropriate postexcisional management treatment should be taken by physicians on a case-by-case basis in order to obtain the best cosmetically acceptable results.

Burns. 2009 Jun 11; Rorison P, Thomlinson A, Hassan Z, Roberts SA, Ferguson MW, Shah MTransforming growth factor beta1, a multifunctional growth factor, plays a pivotal role in wound healing and has been shown to accelerate impaired wound healing. However, high systemic levels of Transforming growth factor beta1 have generally been associated with fibrotic disease processes such as myelofibrosis and pulmonary fibrosis. Hypertrophic scarring occurring during childhood interferes with growth, impairs the function and causes immense psychological and aesthetic problems. Burns is the leading cause of hypertrophic scarring. We studied the longitudinal relationship between plasma Transforming growth factor beta-1 and post-burn wound healing and scarring in children. We discovered that the plasma levels of Transforming growth factor beta-1 rapidly increased to significantly higher levels in the first two weeks post-injury and fell thereafter, in patients who healed with good quality scars post-burn. By contrast, the increase in plasma TGFbeta(1) levels in the early stages after-burn, was noticeably absent in patients who developed hypertrophic scarring. We propose that this change in the systemic levels of TGFbeta(1) early after the burn may be used as an indicator of patients at risk of developing hypertrophic burn scars. This group of patients could then be targeted for early pharmacological/physical interventions to reduce/prevent scar-related morbidity in burn survivors.

Can J Physiol Pharmacol. 2009 Jun; 87(6): 460-70Lajoie C, El-Helou V, Proulx C, Clément R, Gosselin H, Calderone ARapamycin represents a recognized drug-based therapeutic approach to treat cardiovascular disease. However, at least in the female heart, rapamycin may suppress the recruitment of putative signalling events conferring cardioprotection. The present study tested the hypothesis that rapamycin-sensitive signalling events contributed to the cardioprotective phenotype of the female rat heart after an ischemic insult. Rapamycin (1.5 mg/kg) was administered to adult female Sprague-Dawley rats 24 h after complete coronary artery ligation and continued for 6 days. Rapamycin abrogated p70S6K phosphorylation in the left ventricle of sham rats and the noninfarcted left ventricle (NILV) of 1-week postmyocardial-infarcted (MI) rats. Scar weight (MI 0.028 +/- 0.006, MI+rapamycin 0.064 +/- 0.004 g) and surface area (MI 0.37 +/- 0.08, MI+rapamycin 0.74 +/- 0.03 cm2) were significantly larger in rapamycin-treated post-MI rats. In the NILV of post-MI female rats, rapamycin inhibited the upregulation of eNOS. Furthermore, the increased expression of collagen and TGF-beta3 mRNAs in the NILV were attenuated in rapamycin-treated post-MI rats, whereas scar healing was unaffected. The present study has demonstrated that rapamycin-sensitive signalling events were implicated in scar formation and reactive fibrosis. Rapamycin-mediated suppression of eNOS and TGF-beta3 mRNA in post-MI female rats may have directly contributed to the larger infarct and attenuation of the reactive fibrotic response, respectively.

Cell Transplant. 2009 May 6; Drowley L, Okada M, Payne TR, Botta G, Oshima H, Keller BB, Tobita K, Huard JWe have previously shown that populations of skeletal muscle-derived stem cells (MDSCs) exhibit sex-based differences for skeletal muscle and bone repair, with female cells engrafting better than males in skeletal muscle while male cells differentiate more robustly toward the osteogenic and chondrogenic lineages. In this study, we tested the hypothesis that the therapeutic capacity of MDSCs transplanted into myocardium is influenced by sex of donor MDSCs or recipient. Male and female MDSCs isolated from the skeletal muscle of 3 week old mice were transplanted into recipient male or female dystrophin-deficient (mdx) hearts or into the hearts of male SCID mice following acute myocardial infarction. In the mdx model, no difference was seen in engraftment or blood vessel formation based on donor cell or recipient sex. In the infarction model, MDSC transplanted hearts showed higher post-infarction angiogenesis, less myocardial scar formation, and improved cardiac function compared to vehicle controls. However, sex of donor MDSCs had no significant effects on engraftment, angiogenesis, and cardiac function. VEGF expression, a potent angiogenic factor, was similar between male and female MDSCs. Our results suggest that donor MDSC or recipient sex has no significant effect on the efficiency of MDSC-triggered myocardial engraftment or regeneration following cardiac injury. The ability of the MDSCs to improve cardiac regeneration and repair through promotion of angiogenesis without differentiation into the cardiac lineage may have contributed to the lack of sex difference observed in these models.

Cell Transplant. 2009 May 13; Martens TP, Godier AF, Parks JJ, Wan LQ, Koeckert MS, Eng GM, Hudson BI, Sherman W, Vunjak-Novakovic GHeart disease is the leading cause of death in the U.S. Following an acute myocardial infarction, a fibrous, noncontractile scar develops, and results in congestive heart failure in more than 500,000 patients in the U.S. each year. Muscle regeneration and the induction of new vascular growth to treat ischemic disorders of the heart can have significant therapeutic implications. Early studies in patients with chronic ischemic SLVD using skeletal myoblasts or bone marrow-derived cells report improvement in left ventricular ejection function (LVEF) and clinical status, without notable safety issues. Nonetheless, the efficacy of cell-transfer for cardiovascular disease is not established, in part due to a lack of control over cell retention, survival and function following their delivery. We studied the use of biocompatible hydrogels polymerizable in situ as a cell delivery vehicle, to improve cell retention, survival, and function following delivery into the ischemic myocardium. The study was conducted using human bone marrow derived mesenchymal stem cells and fibrin glue, but the methods are applicable to any human stem cells (adult or embryonic) and a wide range of hydrogels. We first evaluated the utility of several commercially available percutaneous catheters for delivery of viscous cell-hydrogel suspensions. Next we characterized the polymerization kinetics of fibrin glue solutions to define the ranges of concentrations compatible with catheter delivery. We then demonstrate the in vivo effectiveness of this preparation and its ability to increase cell retention and survival in a nude rat model of myocardial infarction.

Burns. 2009 Jun 3; Liu T, Wang D, Qian Y, Shi Y, Guan WThis article aims to solve the problem of postburn talipes equinovarus associated with bone and joint pathologic changes by simplified and modified techniques. In addition to lengthening the shortened Achilles tendon and the contracted scar above it, we performed triple arthrodesis directly on the densely scarred, deformed foot without replacing the scar tissue with normal tissue tube or flap. Only the proximal scar-periosteum wound edge of the curved incision, 2cm distal to the conventional one, was elevated to expose the bones to be excised. The two excised wedge-shaped bone blocks, one on the dorsum and the other on the lateral side of the deformed foot, were composed of a larger part of the talus and lesser parts of the navicular, cuboid and calcaneus bones. All the patients who could not stand or walk without crutches pre-operatively obtained a good operative result, which enabled them to do so without crutches postoperatively. We conclude that the scar tissue can be elevated without risk of necrosis if it is still attached firmly to the underlying periosteum, and arthrodesis can be done under it. Incision wound healing and bone union is not exclusively a problem.

Eye Contact Lens. 2009 Jun 4; Prasher P, Muftuoglu O, Bowman RW, McCulley JP, Petroll WM, Cavanagh HD, Mootha VVPURPOSE:: To evaluate the changes in the corneal stroma after Descemet stripping automated endothelial keratoplasty (DSAEK) using tandem scanning confocal microscopy (CM). METHODS:: Thirteen eyes of 13 patients who underwent DSAEK without preoperative corneal haze or scar obvious at the slit lamp, any ocular disease, and postoperative complication were included in the study. All patients were examined clinically and by CM 6 months after DSAEK. RESULTS:: Six months after DSAEK, none of the eyes had clinically significant interface haze (i.e., haze affecting quantity or quality of vision) at slit lamp. The mean best spectacle corrected visual acuity was 0.18 +/- 0.12 (range 0-0.4) logMAR (Snellen 20/30). The CM revealed highly reflective particles in interface in six eyes, particles with mild surrounding increased reflectivity in four eyes, and no discernible interface in three eyes. The mean particles density at interface was 28.6 +/- 23.4 particles/mm. No significant keratocyte activation was seen in any case at the interface. The mean anterior stromal reflectivity was 431.2 +/- 269.1 confocal back scatter units (CBU) and the mean interface reflectivity was 65.9 +/- 46.9 CBU. The mean anterior stromal reflectivity was significantly greater than the mean interface reflectivity (P

Klin Oczna. 2009; 111(1-3): 62-5Kwiecien S, Ulińska M, Sulak R, Szaflik JFriedrich Best described in 1905 for the first time a genetic disease which is subject to autosomal dominant inheritance. Yellow material is assembled under pigment epithelium, especially in the macula. Afterwards pigment epithelium and choroid become involved in the process and visual acuity decreases. In the last phase the fibrotic scar appears in the macula with deterioration of visual acuity. In some late cases choroidal neovascularization develops too. We present a two-generation-family which suffers from Best's disease. Our patients: mother, her daughter and her son demonstrate changes in different phases of development. In mother's case we found fibrotic scar and atrophy of pigment epithelium, which is typical of the late phase of the disease. Daughter complained of decrease in visual acuity, the subretinal neovascularisation was found in the macula and photodynamic therapy was performed. Visual acuity improved from 0.5 to 0.8 and has been stable for 11 months. Son did not report any symptoms. Some yellow material was found under the macula in both eyes without decrease of visual acuity. Described case shows importance of the whole family members' examination in case of Best's disease. Early diagnosis of this serious disease makes possibility of proper treatment.

Bratisl Lek Listy. 2009; 110(3): 197-9Ozalp N, Akgul O, Dizen H, Gocmen E, Keskek M, Tez M, Koc MBACKGROUND: The parasitic infection hydatidosis or echinococcosis, is a parasitic infection caused most frequently by flatworm Echinococcus granulosus. Hydatidosis is endemic in Turkey where animal husbandry is common. Eventhough, Hydatid disease can develop anywhere in the human body it is most frequently occurs in the liver and then the lungs. Rupture of hydatid cysts into the peritoneal cavity, although rare, still presents a challenge for the surgeon. CASE: A 20-year-old man presented with ileus after 24 hours of mild abdominal distention, pain and nausea. On examination his abdomen was tender, with guarding and rebound tenderness and had a 3 cm long subcostal incision scar. All laboratory investigations were in the normal range. Exploratory laparotomy revealed multiple peritoneal cyst hydatid lesions with the largest measuring 10 cm in size and one also located in the right lobe of the liver. CONCLUSIONS: Rupture of hydatid cysts into the peritoneal cavity, although rare, still presents a challenge for the surgeon. This pathology should be included in the differential diagnosis of acute abdomen in endemic areas, especially in patients with a history of cyst hydatid (Fig. 1, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

Asian Cardiovasc Thorac Ann. 2009 Jan; 17(1): 89-101Kao RL, Browder W, Li CRestoring blood flow, improving perfusion, reducing clinical symptoms, and augmenting ventricular function are the goals after acute myocardial infarction. Other than cardiac transplantation, no standard clinical procedure is available to restore damaged myocardium. Since we first reported cellular cardiomyoplasty in 1989, successful outcomes have been confirmed by experimental and clinical studies, but definitive long-term efficacy requires large-scale placebo-controlled double-blind randomized trials. On meta-analysis, stem cell-treated groups had significantly improved left ventricular ejection fraction, reduced infarct scar size, and decreased left ventricular end-systolic volume. Fewer myocardial infarctions, deaths, readmissions for heart failure, and repeat revascularizations were additional benefits. Encouraging clinical findings have been reported using satellite or bone marrow stem cells, but understanding of the benefit mechanisms demands additional studies. Adult mammalian ventricular myocardium lacks adequate regeneration capability, and cellular cardiomyoplasty offers a new way to overcome this; the poor retention and engraftment rate and high apoptotic rate of the implanted stem cells limit outcomes. The ideal type and number of cells, optimal timing of cell therapy, and ideal cell delivery method depend on determining the beneficial mechanisms. Cellular cardiomyoplasty has progressed rapidly in the last decade. A critical review may help us to better plan the future direction.

J Cutan Pathol. 2009 Jul; 36(7): 766-71Ramdial PK, Calonje E, Singh B, Sing Y, Govender PBackground: Even in schistosomiasis-endemic areas, extra-anogenital bilharziasis cutanea tarda (E-BCT) is rare. To date, the occurrence of E-BCT in pre-existing cutaneous pathology is undocumented. The study was undertaken to document the expanded clinicopathological spectrum and to comment on the putative pathogenetic mechanisms of a Schistosoma hematobium-associated E-BCT. Methods: Eight-year clinicopathological appraisal of E-BCT. Results: The clinical details are as follows. Seventeen specimens from 16 patients formed the study cohort. All specimens showed granulomatous inflammation with eosinophils, aggregates of terminal-spined S. hematobium ova and variable fibrosis. Copulating worms were identified in three biopsies. In 12/16 patients, E-BCT occurred in pre-existing pathology, including recurrent squamous papilloma (1), bilateral hidradenitis suppurativa (1) and scar tissue (10) with 7 showing a keloidal morphology. Prior and current urinary schistosomiasis was present in nine and seven patients, respectively. Conclusion: E-BCT, a reflection of prior, re-infective or inadequately treated urinary schistosomiasis, is deemed to be a function of egg-laying consequent to the aberrant pathway of worms. Based on E-BCT occurrence in pre-existing extra-anogenital cutaneous fibroinflammatory and cicatricial processes and the presence of adult worms in three extra-anogenital biopsies in the present study, it is hypothesized that altered tissue mesenchymal repair reactions may promote extra-anogenital cutaneous worm entrapment and egg-laying.

J Cutan Pathol. 2009 Jul; 36(7): 788-92Wang XQ, Chang HE, Francis R, Olszowy H, Liu PY, Kempf M, Cuttle L, Kravchuk O, Phillips GE, Kimble RMBACKGROUND: Silver dressings have been widely and successfully used to prevent cutaneous wounds, including burns, chronic ulcers, dermatitis and other cutaneous conditions, from infection. However, in a few cases, skin discolouration or argyria-like appearances have been reported. This study investigated the level of silver in scar tissue post-burn injury following application of Acticoat, a silver dressing. METHODS: A porcine deep dermal partial thickness burn model was used. Burn wounds were treated with this silver dressing until completion of re-epithelialization, and silver levels were measured in a total of 160 scars and normal tissues. RESULTS: The mean level of silver in scar tissue covered with silver dressings was 136 microg/g, while the silver level in normal skin was less than 0.747 microg/g. A number of wounds had a slate-grey appearance, and dissection of the scars revealed brown-black pigment mostly in the middle and deep dermis within the scar. The level of silver and the severity of the slate-grey discolouration were correlated with the length of time of the silver dressing application. CONCLUSIONS: These results show that silver deposition in cutaneous scar tissue is a common phenomenon, and higher levels of silver deposits and severe skin discolouration are correlated with an increase in the duration of this silver dressing application.

Neurosci Lett. 2009 Jun 8; Nakano T, Iseki K, Hozumi Y, Kawamae K, Wakabayashi I, Goto KDiacylglycerol kinase (DGK) is an enzyme which phosphorylates a second messenger diacylglycerol and consists of a family of isozymes that differ in terms of structural motifs, enzymological property, and cell and tissue distribution. One of the isozymes, DGKzeta was originally shown to be expressed in various kinds of neurons under physiological conditions. However, we unexpectedly found that under pathological conditions, such as cerebral infarction, DGKzeta-immunoreactivity is detected in non-neuronal cells, although it remained to be elucidated in detail which cell types are responsible for the induced expression of DGKzeta in this setting. To further elucidate functional implications of DGKzeta in non-neuronal cells we performed detailed immunohistochemical analysis of DGKzeta using rat brain cryoinjury model. As early as 1h after cryoinjury, DGKzeta-immunoreactivity was greatly decreased in the afflicted cerebral cortex and almost disappeared in the necrotic core. On day 7 after cryoinjury, however, DGKzeta-immunoreactivity reappeared in this area. DGKzeta-immunoreactivity was clearly detected in Iba1-immunoreactive cells of an oval or ameboid shape in the scar region, which represent activated microglia and/or macrophages. On the other hand, DGKzeta-immunoreactivity was not detected in Iba1-immunoreactive, resting microglia of ramified and dendritic configuration in the intact cortex. Furthermore, DGKzeta-immunoreactive cells were also positive for a microglia marker GLUT5 in the scar region, but never for an astrocyte marker GFAP. Taken together, the present study reveals that DGKzeta is induced in activated microglia in brain trauma, suggesting the functional significance of DGKzeta in this process.

Matrix Biol. 2009 Jun 8; Vukovic J, Marmorstein LY, McLaughlin PJ, Sasaki T, Plant GW, Harvey AR, Ruitenberg MJThe adult olfactory epithelium has maintained the ability to reconstitute its olfactory sensory neurons (OSNs) from a basal progenitor cell compartment. This allows for life-long turnover and replacement of receptor components as well as repair of the primary olfactory pathway in response to injury and environmental insults. The present study investigated whether fibulin-3, a glycoprotein in the extracellular matrix and binding partner of tissue inhibitor of metalloproteinases-3 (TIMP-3), plays a role in ongoing plasticity and regenerative events in the primary adult olfactory pathway. In wild-type control mice, fibulin-3 protein was detected on IB4(+)CD31(+) blood vessels, nerve fascicles and the basement membrane underneath the olfactory epithelium. After target ablation (olfactory bulbectomy), fibulin-3 was also abundantly present in central nervous system (CNS) scar tissue that occupied the bulbar cavity. Using two different lesion models, i.e. intranasal Triton X-100 lesion and olfactory bulbectomy, we show that fibulin-3 deficient (Efemp1(-/-)) mice have impaired recovery of the olfactory epithelium after injury. Ten days post-injury, Efemp1(-/-) mice showed altered basal stem/progenitor cell proliferation and increased overall numbers of mature (olfactory marker protein (OMP) -positive) versus immature OSNs. However, compromised regenerative capacity of the primary olfactory pathway in Efemp1(-/-) mice was evidenced by reduced numbers of mature OSNs at the later time point of 42 days post-injury. In addition to these neural differences there were consistent changes in blood vessel structure in the olfactory lamina propria of Efemp1(-/-) mice. Overall, these data suggest a role for fibulin-3 in tissue maintenance and regeneration in the adult olfactory pathway.