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1.
Cleft Palate Craniofac J ; 51(5): 605-12, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24125399

RESUMO

Objective : The learning process for intraoral procedures is arguably more difficult than for other surgical procedures because of the assistant's severely limited visibility. Consequently, trainees may not be able to adequately see and follow all steps of the procedure, and attending surgeons may be less willing to entrust trainees with critical portions of the procedure. In this report, we propose a video-assisted approach to intraoral procedures that improves lighting, visibility, and potential for effective education and training. Design : Technical report (idea/innovation). Setting : Tertiary referral hospital. Patients : Children with cleft palate and velopharyngeal insufficiency requiring surgery. Interventions : Video-assisted palatoplasty, sphincteroplasty, and pharyngoplasty. Main Outcome Measures : Qualitative and semiquantitative educational outcomes, including learner perception regarding "real-time" (video-assisted surgery) and "non-real-time" (video-library-based) surgical education. Results : Trainees were strongly in favor of the video-assisted modality in "real-time" surgical training. Senior trainees identified more opportunities in which they had been safely entrusted to perform critical portions of the procedure, corresponding with satisfaction with the learning process scores, and they showed greater comfort/confidence scores related to performing the procedure under supervision and alone. Conclusions : Adoption of the video-assisted approach can be expected to markedly improve the learning curve for surgeons in training. This is now standard practice at our institution. We are presently conducting a full educational technology assessment to better characterize the effect on knowledge acquisition and technical improvement.


Assuntos
Fissura Palatina/cirurgia , Educação Médica/métodos , Procedimentos Cirúrgicos Bucais/educação , Insuficiência Velofaríngea/cirurgia , Cirurgia Vídeoassistida/educação , Ergonomia , Humanos
2.
FASEB J ; 26(3): 1027-39, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22067482

RESUMO

This study aimed to investigate the mechanisms that coordinate lymphangiogenesis. Using mouse models of lymphatic regeneration and inflammatory lymphangiogenesis, we explored the hypothesis that hypoxia inducible factor-α (HIF-1α) is a central regulator of lymphangiogenesis. We show that HIF-1α inhibition by small molecule inhibitors (YC-1 and 2-methyoxyestradiol) results in delayed lymphatic repair, decreased local vascular endothelial growth factor-C (VEGF-C) expression, reduced numbers of VEGF-C(+) cells, and reductions in inflammatory lymphangiogenesis. Using transgenic HIF-1α/luciferase mice to image HIF-1α expression in real time in addition to Western blot analysis and pimonidazole staining for cellular hypoxia, we demonstrate that hypoxia stabilizes HIF-1α during initial stages of wound repair (1-2 wk); whereas inflammation secondary to gradients of lymphatic fluid stasis stabilizes HIF-1α thereafter (3-6 wk). In addition, we show that CD4(+) cell-mediated inflammation is necessary for this response and regulates HIF-1α expression by macrophages, as CD4-deficient or CD4-depleted mice demonstrate 2-fold reductions in HIF-1α expression as compared to wild-types. In summary, we show that HIF-1α is a critical coordinator of lymphangiogenesis by regulating the expression of lymphangiogenic cytokines as part of an early response mechanism to hypoxia, inflammation, and lymphatic fluid stasis.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Inflamação/fisiopatologia , Linfangiogênese/fisiologia , Cicatrização/fisiologia , Animais , Western Blotting , Antígenos CD4/genética , Antígenos CD4/metabolismo , Hipóxia Celular , Edema/genética , Edema/metabolismo , Edema/fisiopatologia , Feminino , Expressão Gênica , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Indazóis/farmacologia , Inflamação/genética , Inflamação/metabolismo , Linfa/metabolismo , Linfa/fisiologia , Linfangiogênese/efeitos dos fármacos , Linfangiogênese/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Cicatrização/genética
3.
Am J Pathol ; 177(6): 3202-14, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21056998

RESUMO

Lymphedema is a complication of cancer treatment occurring in approximately 50% of patients who undergo lymph node resection. Despite its prevalence, the etiology of this disorder remains unknown. In this study, we determined the effect of soft tissue fibrosis on lymphatic function and the role of transforming growth factor (TGF)-ß1 in the regulation of this response. We determined TGF-ß expression patterns in matched biopsy specimens collected from lymphedematous and normal limbs of patients with secondary lymphedema. To determine the role of TGF-ß in regulating tissue fibrosis, we used a mouse model of lymphedema and inhibited TGF-ß function either systemically with a monoclonal antibody or locally by using a soluble, defective TGF-ß receptor. Lymphedematous tissue demonstrated a nearly threefold increase in the number of cells that stained for TGF-ß1. TGF-ß inhibition markedly decreased tissue fibrosis, increased lymphangiogenesis, and improved lymphatic function compared with controls. In addition, inhibition of TGF-ß not only decreased TGF-ß expression in lymphedematous tissues, but also diminished inflammation, migration of T-helper type 2 (Th2) cells, and expression of profibrotic Th2 cytokines. Similarly, systemic depletion of T-cells markedly decreased TGF-ß expression in tail tissues. Inhibition of TGF-ß function promoted lymphatic regeneration, decreased tissue fibrosis, decreased chronic inflammation and Th2 cell migration, and improved lymphatic function. The use of these strategies may represent a novel means of preventing lymphedema after lymph node resection.


Assuntos
Anticorpos Monoclonais/farmacologia , Linfangiogênese/efeitos dos fármacos , Vasos Linfáticos/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Cicatrização/efeitos dos fármacos , Animais , Células Cultivadas , Feminino , Fibrose/patologia , Humanos , Linfangiogênese/imunologia , Linfangiogênese/fisiologia , Vasos Linfáticos/imunologia , Vasos Linfáticos/metabolismo , Vasos Linfáticos/fisiopatologia , Linfedema/imunologia , Linfedema/metabolismo , Linfedema/patologia , Camundongos , Camundongos Endogâmicos C57BL , Regeneração/imunologia , Regeneração/fisiologia , Células Th2/efeitos dos fármacos , Células Th2/fisiologia , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia , Regulação para Cima/fisiologia , Cicatrização/imunologia , Cicatrização/fisiologia
4.
Glob Heart ; 16(1): 11, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33598391

RESUMO

Background: Low- and-middle-income-countries (LMICs) currently bear 80% of the world's cardiovascular disease (CVD) mortality burden. The same countries are underequipped to handle the disease burden due to critical shortage of resources. Functional cardiac catheterization laboratories (cath labs) are central in the diagnosis and management of CVDs. Yet, most LMICs, including Uganda, fall remarkably below the minimum recommended standards of cath lab:population ratio due to a host of factors including the start-up and recurring costs. Objectives: To review the performance, challenges and solutions employed, lessons learned, and projections for the future for a single cath lab that has been serving the Ugandan population of 40 million people in the past eight years. Methods: A retrospective review of the Uganda Heart Institute cath lab clinical database from 15 February 2012 to 31 December 2019 was performed. Results: In the initial two years, this cath lab was dependent on skills transfer camps by visiting expert teams, but currently, Ugandan resident specialists independently operate this lab. 3,542 adult and pediatric procedures were conducted in 8 years, including coronary angiograms and percutaneous coronary interventions, device implantations, valvuloplasties, and cardiac defect closures, among others. There was a consistent expansion of the spectrum of procedures conducted in this cath lab each year. The initial lack of technical expertise and sourcing for equipment, as well as the continual need for sundries present(ed) major roadblocks. Government support and leveraging existing multi-level collaborations has provided a platform for several solutions. Sustainability of cath lab services remains a significant challenge especially in relation to the high cost of sundries and other consumables amidst a limited budget. Conclusion: A practical example of how centers in LMIC can set up and sustain a public cardiac catheterization laboratory is presented. Government support, research, and training collaborations, if present, become invaluable leverage opportunities.


Assuntos
Cateterismo Cardíaco , Laboratórios , Adulto , Catéteres , Criança , Humanos , Estudos Retrospectivos , Uganda/epidemiologia
5.
Am J Physiol Cell Physiol ; 299(3): C589-605, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20519446

RESUMO

Although radiation therapy is a major risk factor for the development of lymphedema following lymphadenectomy, the mechanisms responsible for this effect remain unknown. The purpose of this study was therefore to determine the effects of radiation on lymphatic endothelial cells (LECs) and lymphatic function. The tails of wild-type or acid sphingomyelinase (ASM)-deficient mice were treated with 0, 15, or 30 Gy of radiation and then analyzed for LEC apoptosis and lymphatic function at various time points. To analyze the effects of radiation fibrosis on lymphatic function, we determined the effects of transforming growth factor (TGF)-beta1 blockade after radiation in vivo. Finally, we determined the effects of radiation and exogenous TGF-beta1 on LECs in vitro. Radiation caused mild edema that resolved after 12-24 wk. Interestingly, despite resolution of tail edema, irradiated animals displayed persistent lymphatic dysfunction. Radiation caused loss of capillary lymphatics and was associated with a dose-dependent increase in LEC apoptosis. ASM-/- mice had significantly less LEC apoptosis; however, this finding did not translate to improved lymphatic function at later time points. Short-term blockade of TGF-beta1 function after radiation markedly decreased tissue fibrosis and significantly improved lymphatic function but did not alter LEC apoptosis. Radiation therapy decreases lymphatic reserve by causing depletion of lymphatic vessels and LECs as well as promoting soft tissue fibrosis. Short-term inhibition of TGF-beta1 activity following radiation improves lymphatic function and is associated with decreased soft tissue fibrosis. ASM deficiency confers LEC protection from radiation-induced apoptosis but does not prevent lymphatic dysfunction.


Assuntos
Vasos Linfáticos/efeitos da radiação , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/fisiopatologia , Pele/efeitos da radiação , Fator de Crescimento Transformador beta1/fisiologia , Animais , Apoptose/efeitos da radiação , Linhagem Celular , Senescência Celular/efeitos da radiação , Colágeno/biossíntese , Células Endoteliais/patologia , Células Endoteliais/fisiologia , Células Endoteliais/efeitos da radiação , Fibrose , Humanos , Vasos Linfáticos/patologia , Vasos Linfáticos/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Lesões Experimentais por Radiação/etiologia , Radioterapia/efeitos adversos , Proteínas Recombinantes/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Esfingomielina Fosfodiesterase/genética , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/farmacologia , Proteínas de Transporte Vesicular/biossíntese
6.
Ann Surg Oncol ; 17(11): 2926-32, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20499284

RESUMO

BACKGROUND: Recent reports have demonstrated that lymphedema can occur after even minor pertubation of the axillary region such as sentinel lymph node biopsy (SLNB). The impact of breast reconstruction on the development of lymphedema, however, remains unknown. Therefore, the purpose of this study was to determine the impact of immediate tissue expander breast reconstruction on the risk of developing lymphedema. MATERIALS AND METHODS: We identified patients who had undergone mastectomy with SLNB or SLNB and axillary lymph node dissection (ALND) with or without breast reconstruction using our prospectively maintained lymphedema and breast reconstruction databases. The development of lymphedema was evaluated prospectively using arm measurements and a validated questionnaire. Associations between variables were examined. Logistic regression was used to examine the association of reconstruction on prevalence of lymphedema while adjusting individually for BMI, age, and weight gain after surgery. RESULTS: Characteristics of patients with or without reconstruction were similar except for age, BMI, and weight gain since surgery. Median follow-up was 5 years. Among patients treated with mastectomy with SLNB or SLNB/ALND, those undergoing reconstruction had a lower rate of measured lymphedema than those who did not (5% vs. 18%, P < .0004). The reconstructed group also had fewer patients with both measured and self-reported lymphedema (3% vs. 12%, P < .002). Differences in the rates of measured lymphedema between groups persisted following univariate logistical regression for differences in age, BMI, and weight gain. CONCLUSIONS: Tissue expander breast reconstruction in patients undergoing SLNB or SLNB/ALND does not increase the risk of developing measured or perceived lymphedema.


Assuntos
Neoplasias da Mama/cirurgia , Linfedema/etiologia , Mamoplastia/efeitos adversos , Dispositivos para Expansão de Tecidos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/patologia , Feminino , Humanos , Modelos Logísticos , Excisão de Linfonodo , Mastectomia , Fatores de Risco
7.
Breast J ; 16(6): 639-43, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21121083

RESUMO

Chronic post-surgical lymphedema is common condition that afflicts nearly 2 million Americans. In the USA, it is most commonly encountered in the upper extremities of patients who have undergone axillary lymph node dissection for breast cancer. Lymphedema has a significant negative effect on cosmesis, limb function, and overall quality of life. Despite the impact of this condition, very little is known about how to effectively prevent or treat lymphedema. While therapeutic options for chronic extremity lymphedema remain limited, several surgical approaches have been suggested. These include techniques aimed at reducing limb volume, as well as techniques that aim to reconstitute disrupted lymphatic channels. Operations proposed to re-establish lymphatic continuity include lymphatico-venous anastomoses, lymphatico-lymphatico anastomoses, and tissue transfer.


Assuntos
Sistema Linfático/anatomia & histologia , Sistema Linfático/fisiologia , Linfedema/etiologia , Complicações Pós-Operatórias/etiologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Sistema Linfático/cirurgia , Regeneração
8.
Surg Endosc ; 22(10): 2168-70, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18626708

RESUMO

BACKGROUND: The natural history of colostomies and ileostomies for colonic disease is not well described. This study aimed to identify factors that have an impact on colostomy and ileostomy reversal among patients with colonic diseases. METHODS: A retrospective review of patients with ileostomies and colostomies was performed at a university hospital from 1999 to 2005. Demographic, operative, and outcome data were collected. Data were analyzed using analysis of variance (ANOVA), t-test, and descriptive statistics. Mantel-Haenstel chi-square was used to establish association (p<0.05). RESULTS: There were 96 patients (49 women) with an overall mean age of 56 years at the time of ostomy creation. Ostomy reversal was performed for 35 patients after an average interval of 5.6 months (range, 12-432 days). The patients' ages were significantly different between the reversed and nonreversed groups (p=0.01). The mean age was 49.9 years for the reversed group and 60.5 years for the nonreversed group. In a logistic regression model including demographic variables, African Americans were four times less likely to undergo reversal than Caucasians [odds ratio (OR), 0.24; 95% confidence interval (CI), 0.075-0.794]. Loop ileostomies (p=0.05) and sigmoid colostomies (p=0.01) were the only types of ostomies that demonstrated a significant association with reversal. Loop ileostomy was five times more likely to be reversed than sigmoid colostomy (OR, 0.17; 95% CI, 0.049-0.595). CONCLUSIONS: Colostomy or ileostomy creation is a basic skill in the armamentarium of the general surgeon for treating complex diseases of the colon. Age, race, and type of ostomy creation are significant predictors for reversal. This data may be useful for consulting patients preoperatively regarding postoperative expectations.


Assuntos
Colostomia/estatística & dados numéricos , Ileostomia/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
J Pediatr Orthop B ; 15(2): 87-92, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16436941

RESUMO

We performed a retrospective, nonrandomized cohort study of unilateral, chronic, severe, stable slipped capital femoral epiphysis comparing five girls and five boys who underwent in-situ screw fixation alone with five girls and five boys who underwent in-situ screw fixation combined with staged flexion intertrochanteric femoral osteotomy to restore proximal femoral alignment. Functional outcome was measured by the Harris hip score, with 20% selected as a goal for improvement in functional outcome after corrective osteotomy. While flexion intertrochanteric femoral osteotomy improved hip range of motion, we found no significant difference in functional outcome between the two groups at early follow-up. This is a level 3 evidence study.


Assuntos
Epifise Deslocada/fisiopatologia , Epifise Deslocada/cirurgia , Cabeça do Fêmur/fisiopatologia , Cabeça do Fêmur/cirurgia , Osteotomia/métodos , Adolescente , Parafusos Ósseos , Criança , Avaliação da Deficiência , Epifise Deslocada/patologia , Feminino , Cabeça do Fêmur/patologia , Seguimentos , Humanos , Fixadores Internos , Masculino , Osteotomia/instrumentação , Estudos Retrospectivos , Método Simples-Cego , Resultado do Tratamento
10.
Plast Reconstr Surg Glob Open ; 3(9): e514, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26495227

RESUMO

BACKGROUND: Peripheral vascular surgery may be complicated by wound infection and potential graft exposure in the groin area. Muscle flap coverage of the graft has been promoted to address these wound complications. The authors present their findings regarding graft salvage rates and patient outcomes using local muscle flaps to address vascular graft complications of the groin. METHODS: Data were obtained by retrospective cohort study of patients who underwent a local muscle flap procedure by a single surgeon following vascular graft complication in the groin. RESULTS: Seventeen patients undergoing local muscle flap coverage of a vascular graft were reviewed. Six men and 9 women, 51-80 years old, were included in the study. Wound complications in the groin occurred anywhere from 3 days to 3.5 years following graft placement. Graft exposure was the most common presenting complication (14 of 17 patients). Muscle flap coverage occurred within 15 days of complication presentation in all patients (average, 6.4 days). Seven of the 15 patients experienced postoperative complications within 6 months of the procedure, most commonly wound dehiscence. However, analysis demonstrated that vascular grafts were successfully salvaged in 10 of the 17 patients (59%) over the course of follow-up (range, 104-1748 days). Average time to muscle flap coverage was 4.2 days in patients who retained the graft and 9.6 days in patients who ultimately lost their vascular graft. CONCLUSION: The authors demonstrate improved vascular graft salvage rate when local muscle flap procedure is performed early after initial wound complication presentation.

11.
J Plast Reconstr Aesthet Surg ; 66(1): 113-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23026473

RESUMO

Achilles tendon and soft-tissue contractures caused by trauma to the foot and ankle are complex injuries. An array of techniques, including local and distant flaps, has been used and described to reconstruct these challenging wounds. However, the management of these injuries in a growing child who develops abnormal gait due to equinus deformity has not been categorically reported. The latissimus dorsi myocutaneous flap has the advantage of a rich blood supply making specific partial muscle harvest possible. In this case series, we report on five paediatric patients with severe contracture of the Achilles tendon and posterior ankle, who were reconstructed with free partial latissimus dorsi myocutaneous flaps. All flaps survived and satisfactory form and function of the ankle joint were achieved with minimal donor morbidity. We believe that the free partial latissimus dorsi myocutaneous flap is an excellent option for the soft-tissue reconstruction of severe Achilles tendon contracture in children.


Assuntos
Pé Equino/cirurgia , Retalhos de Tecido Biológico , Músculo Esquelético/transplante , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele , Tendão do Calcâneo/lesões , Tendão do Calcâneo/cirurgia , Adolescente , Traumatismos do Tornozelo/complicações , Traumatismos do Tornozelo/cirurgia , Criança , Contratura/etiologia , Contratura/cirurgia , Pé Equino/etiologia , Feminino , Seguimentos , Marcha , Humanos , Masculino , Ombro/fisiopatologia , Ombro/cirurgia
12.
Plast Reconstr Surg ; 124(2): 438-450, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19644258

RESUMO

BACKGROUND: Lymphedema is a common debilitating sequela of lymph node dissection. Although numerous clinical studies suggest that factors that lead to fibrosis are associated with the development of lymphedema, this relationship has not been proven. The purpose of these experiments was therefore to evaluate lymphatic regeneration in the setting of variable soft-tissue fibrosis. METHODS: A section of mouse tail skin including the capillary and collecting lymphatics was excised. Experimental animals (n = 20) were treated with topical collagen type I gel and a moist dressing, whereas control animals (n = 20) underwent excision followed by moist dressing alone. Fibrosis, acute lymphedema, lymphatic function, gene expression, lymphatic endothelial cell proliferation, and lymphatic fibrosis were evaluated at various time points. RESULTS: Collagen gel treatment significantly decreased fibrosis, with an attendant decrease in acute lymphedema and improved lymphatic function. Tails treated with collagen gel demonstrated greater numbers of lymphatic vessels, more normal lymphatic architecture, and more proliferating lymphatic endothelial cells. These findings appeared to be independent of vascular endothelial growth factor C expression. Decreased fibrosis was associated with a significant decrease in the expression of extracellular matrix components. Finally, decreased soft-tissue fibrosis was associated with a significant decrease in lymphatic fibrosis as evidenced by the number of lymphatic endothelial cells that coexpressed lymphatic and fibroblast markers. CONCLUSIONS: Soft-tissue fibrosis is associated with impairment in lymphatic regeneration and lymphatic function. These defects occur as a consequence of impaired lymphatic endothelial cell proliferation, abnormal lymphatic microarchitecture, and lymphatic fibrosis. Inhibition of fibrosis using a simple topical dressing can markedly accelerate lymphatic repair and promote regeneration of normal capillary lymphatics.


Assuntos
Vasos Linfáticos/fisiopatologia , Regeneração/fisiologia , Animais , Proliferação de Células , Colágeno Tipo I/administração & dosagem , Células Endoteliais/fisiologia , Feminino , Fibrose , Géis , Imuno-Histoquímica , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Linfedema/fisiopatologia , Camundongos , Camundongos Endogâmicos , Modelos Animais , Reação em Cadeia da Polimerase , Cauda , Fator C de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/fisiologia
13.
Am J Physiol Heart Circ Physiol ; 295(5): H2113-27, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18849330

RESUMO

Although clinical studies have identified scarring/fibrosis as significant risk factors for lymphedema, the mechanisms by which lymphatic repair is impaired remain unknown. Transforming growth factor -beta1 (TGF-beta1) is a critical regulator of tissue fibrosis/scarring and may therefore also play a role in the regulation of lymphatic regeneration. The purpose of this study was therefore to assess the role of TGF-beta1 on scarring/fibrosis and lymphatic regeneration in a mouse tail model. Acute lymphedema was induced in mouse tails by full-thickness skin excision and lymphatic ligation. TGF-beta1 expression and scarring were modulated by repairing the wounds with or without a topical collagen gel. Lymphatic function and histological analyses were performed at various time points. Finally, the effects of TGF-beta1 on lymphatic endothelial cells (LECs) in vitro were evaluated. As a result, the wound repair with collagen gel significantly reduced the expression of TGF-beta1, decreased scarring/fibrosis, and significantly accelerated lymphatic regeneration. The addition of recombinant TGF-beta1 to the collagen gel negated these effects. The improved lymphatic regeneration secondary to TGF-beta1 inhibition was associated with increased infiltration and proliferation of LECs and macrophages. TGF-beta1 caused a dose-dependent significant decrease in cellular proliferation and tubule formation of isolated LECs without changes in the expression of VEGF-C/D. Finally, the increased expression of TGF-beta1 during wound repair resulted in lymphatic fibrosis and the coexpression of alpha-smooth muscle actin and lymphatic vessel endothelial receptor-1 in regenerated lymphatics. In conclusion, the inhibition of TGF-beta1 expression significantly accelerates lymphatic regeneration during wound healing. An increased TGF-beta1 expression inhibits LEC proliferation and function and promotes lymphatic fibrosis. These findings imply that the clinical interventions that diminish TGF-beta1 expression may be useful in promoting more rapid lymphatic regeneration.


Assuntos
Linfangiogênese , Vasos Linfáticos/fisiopatologia , Linfedema/fisiopatologia , Pele/fisiopatologia , Fator de Crescimento Transformador beta1/metabolismo , Cicatrização , Administração Cutânea , Animais , Movimento Celular , Proliferação de Células , Cicatriz/metabolismo , Cicatriz/fisiopatologia , Colágeno/administração & dosagem , Procedimentos Cirúrgicos Dermatológicos , Endotélio Linfático/metabolismo , Endotélio Linfático/fisiopatologia , Feminino , Fibroblastos/metabolismo , Fibrose , Géis , Ligadura , Linfangiogênese/efeitos dos fármacos , Vasos Linfáticos/efeitos dos fármacos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Vasos Linfáticos/cirurgia , Linfedema/metabolismo , Linfedema/patologia , Linfedema/prevenção & controle , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Cauda , Fatores de Tempo , Cicatrização/efeitos dos fármacos
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