RESUMO
Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies. However, skin explants have a limited life span. In an attempt to overcome this problem, we used an innovative bioreactor that allowed us to achieve good structural and functional preservation in vitro of explanted human skin for up to 72 h. This device was then used to set up an in vitro inflammatory model by applying two distinct agents mimicking either exogenous or endogenous stimuli: i.e., dithranol, inducing the contact dermatitis phenotype, and the substance P, mimicking neurogenic inflammation. Our in vitro system proved to reproduce inflammatory events observed in vivo, such as vasodilation, increased number of macrophages and mast cells, and increased cytokine secretion. This bioreactor-based system may therefore be suitably and reliably used to simulate in vitro human skin inflammation and may be foreseen as a promising tool to test the efficacy of drugs and cosmetics.
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Hidrodinâmica , Pele , Humanos , Pele/metabolismo , Administração Cutânea , Absorção Cutânea , Inflamação/metabolismo , Preparações Farmacêuticas/metabolismoRESUMO
In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9% w/w and transethosomes based on phosphatidylcholine 0.9 or 2.7% w/w plus polysorbate 80 0.3% w/w as an edge activator were prepared and characterized. The vesicle mean size, morphology and deformability were influenced by both phosphatidylcholine and polysorbate 80. Indeed, the mean diameters of ethosome were around 200 nm, while transethosome's mean diameters were 146 or 350 nm in the case of phosphatidylcholine 0.9 or 2.7%, w/w, respectively. The highest deformability was achieved by transethosomes based on phosphatidylcholine 0.9%, w/w. The three types of vesicular nanosystems were applied on explanted human skin maintained in a bioreactor. Transmission electron microscopy demonstrated that all vesicles were able to enter the skin, keeping their structural integrity. Notably, the vesicle penetration capability was influenced by their physical-chemical features. Indeed, ethosomes reached keratinocytes and even the dermis, phosphatidylcholine 0.9% transethosomes were found in keratinocytes and phosphatidylcholine 2.7% transethosomes were found only in corneocytes of the outer layer. These findings open interesting perspectives for a differentiated application of these vesicles for transdermal drug delivery as a function of the cutaneous pathology to be addressed.
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Portadores de Fármacos , Absorção Cutânea , Humanos , Portadores de Fármacos/química , Pele/metabolismo , Administração Cutânea , Fosfatidilcolinas/metabolismo , Lipossomos/químicaRESUMO
BACKGROUND: The superior (SGA) and the inferior gluteal artery (IGA) perforator flaps are widely used in pressure-sore repair and in breast reconstruction. The aim was to exhaustively depict the topographical anatomy of the whole system of perforators in the buttock. METHODS: Eighty lower-extremity computed tomographic angiography (CTA) of patients (20 males/20 females, mean age 61-years old, range 38-81) were considered. The source artery, location, type, and caliber of gluteal perforators were analyzed. The location of perforators was reproduced using a standardized two-dimensional grid on the coronal plane, centered onto defined bone landmarks. We defined "radiosome" the cutaneous vascular territory of a source artery inferred through the representation of its whole perforator system at the exit point through the deep fascia. RESULTS: A mean number of 25.6 ± 5.7 perforators in the gluteal region was observed, distributed as follows: 11.6 ± 4.8(45.2%) from SGA; 7.9 ± 4.5(30.8%) from IGA; 1.5 ± 0.8(5.8%) from fifth lumbar artery; 1.2 ± 0.8(4.7%) from internal pudendal artery; 1.2 ± 1(4.8%) from lateral circumflex femoral artery; 0.3 ± 0.7(1.2%) from circumflex iliac superficial artery. At least one large (internal diameter > 1 mm) SGA septocutaneous perforator was present in 77.5% of patients. CONCLUSIONS: The gluteal region is vascularized by perforators of multiple source arteries. Septocutaneous perforators of SGA and IGA were planned along a curve drawn from the posterior-superior border of the iliac crest to the greater trochanter. The lumbar artery perforators are clustered over the apex of the iliac crest; the internal pudendal artery perforators are clustered medially to the ischiatic tuberosity. Contributions can also come from the sacral and superficial circumflex iliac arteries.
Assuntos
Nádegas/irrigação sanguínea , Angiografia por Tomografia Computadorizada , Retalho Perfurante/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Nádegas/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Background: Selective bromelain-based enzymatic debridement (BED) has emerged as a valid alternative for the treatment of extensive burns, with Total Body Surface Area (TBSA) > 20%. Autologous skin grafting represents the procedure of choice but the scarcity of donor sites remains the main reconstructive challenge. The modified Meek micro-grafting technique may represent a valid strategy to optimize the final outcome. Methods: A single-cohort retrospective analysis was performed, involving nine burn patients (TBSA > 20%) who underwent both BED and subsequently modified Meek technique. Demographic and clinical data (mechanism of injury, surgical treatment, complications, necessity of re-grafting, further surgery and esthetic outcome) were collected. Results: All patients had large burns of mixed and deep dermal thickness (first, second, and third degree). All burns were enzymatically debrided postadmission and covered by the modified Meek technique. Local infection due to poor general conditions was the main complication for all patients. All but two patients survived. The selectiveness of the enzymatic debridement and dermal preservation seemed to improve the quality of scars resulting from micro-grafting. Evaluations performed at 12 ± 2 months postburn showed superior scar quality compared to areas treated with traditional (sheet/mesh) grafts. Conclusion: Combined BED and Meek techniques may provide an effective synergic combination for the treatment of extensive burns.
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OBJECTIVE: To present a new surgical technique on the basis of an internal thigh fasciocutaneous flap for generating a compliant and sensitive neovagina with preservation of the external genitalia. DESIGN: Video demonstration of the surgical steps. PATIENT(S): An 18-year-old woman with Müllerian agenesis confirmed at ultrasound and magnetic resonance imaging. The residual vagina was 3 cm long and 1.5 cm wide. After counseling by a gynecologist and plastic surgeon, in which all available techniques with pros and cons were exposed, the patient opted for the new technique. The long time required by conservative approaches and the desire to preserve the external genitalia with the chance to have a sensitive vagina guided the choice. INTERVENTION(S): The cul-de-sac of the vaginal stump was incised transversally. A 4-cm-wide and 9-cm-long canal bounded anteriorly by the bladder, posteriorly by the rectum, and superiorly by the peritoneum of Douglas was developed by blunt dissection. Fasciocutaneous flaps of 12 per 5 cm on the anteromedial aspect of the thighs were developed, identifying the vascular-from the pudendal artery-and nervous pedicles. A tunnel between the flap pedicles and neovagina introitus was created between fascia and subcutaneous tissue, detaching the vulvar structures from the ischiopubic ramus. Flaps were tunneled up to the neovagina introitus and sutured together by interrupted suture to form a tube with outside skin. The flaps were transposed into the canal everting the tube to obtain the skin lining the internal neovagina. The inferior margins of the flaps were sutured to the vaginal stump mucosa. No internal stitches were placed. Antibiotic prophylaxis was used during surgery. The entire procedure lasted 6 hours. During the postoperative period, no special positioning or ambulation restrictions were used. MAIN OUTCOME MEASURE(S): Compliance and sensitivity of the neovagina, esthetic result, and perioperative and long-term complications. RESULT(S): The postoperative course was uneventful, with early mobilization. The length of hospital stay was 16 days to allow proper vaginal dilator use; initial daily followed by intermittent use was planned. At a 2-year follow-up, the neovagina was sensitive and patent, allowing sexual intercourse. No complications were reported, and the patient was satisfied with the functional and esthetic result. CONCLUSION(S): The new surgical technique was feasible and effective, preserving the external genitalia and avoiding graft healing and bowel secretion drawbacks without an intra-abdominal surgical step and related risks. However, more cases-2 cases performed to date with similar results-and long-term follow-up are needed to confirm the efficacy. In this regard, the regular use of vaginal dilators and forecast adherence between flaps and the connective tissue of the bladder and rectum are expected to prevent neovagina prolapse without any anchoring to the pelvic structures.
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Transtornos 46, XX do Desenvolvimento Sexual , Ductos Paramesonéfricos , Retalhos Cirúrgicos , Vagina , Humanos , Feminino , Vagina/cirurgia , Vagina/anormalidades , Adolescente , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/cirurgia , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Anormalidades Congênitas/cirurgia , Estruturas Criadas Cirurgicamente , Procedimentos Cirúrgicos em Ginecologia/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Shockwave (SW) application has been shown to limit flap necrosis. However, the underlying microhemodynamic mechanisms remain unclear. Therefore, the objective of this study was to analyze the effect of SW application on a microcirculatory level. METHODS: We treated 12 C57BL/6 mice with local SW application (500 shockwave impulses at 0.15 mJ/mm(2)) either 24 h before (preconditioning [PRE]) or 30 min after (postconditioning [POST]) flap elevation. Animals with an untreated flap (CON) or without a flap served as controls. We applied dorsal skinfold chambers to the animals and performed epifluorescence microscopy over a 10-d period to assess microcirculatory parameters (arteriolar diameter, red blood cell velocity, blood flow, functional capillary density, and intercapillary distance) as well as inflammation, apoptotic cell death, and necrosis. RESULTS: SW application significantly decreased tissue necrosis independently of the application time point (PRE: 29% ± 7%; POST: 25% ± 7% versus CON: 47% ± 2%; day 10, P < 0.05). Arteriolar diameter, red blood cell velocity, and blood flow were not statistically significantly different among the 3 flap groups. However, SW (PRE and POST) resulted in an early and persistent increase in functional capillary density and consequently decreased intercapillary distance compared with CON and the group without a flap (P < 0.05). Also, SW resulted in a significantly decreased inflammatory response (P < 0.05) and induced an angiogenic response, as indicated by new functional microvessel formation observed 5 d after therapy. CONCLUSIONS: Local SW application improved tissue survival by recruitment of sleeping capillaries within the non ischemic tissue and maintenance of capillary perfusion within the critically perfused tissue after induction of ischemia, which was independent of the application time point. Neoangiogenesis occurred beyond the ischemic tolerance of the tissue, and therefore does not seem to contribute to improved tissue survival.
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Capilares/fisiologia , Ondas de Choque de Alta Energia/uso terapêutico , Neovascularização Fisiológica/fisiologia , Pele/irrigação sanguínea , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Procedimentos Cirúrgicos Dermatológicos , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/fisiologia , Modelos Animais , Necrose , Fluxo Sanguíneo Regional/fisiologia , Pele/patologiaRESUMO
BACKGROUND: Breast reconstruction after mastectomy using silicone implants is a surgical procedure that occasionally leads to capsular contracture formation. This phenomenon constitutes an important and persistent cause of morbidity, and no successful therapies are available to date. Recently, the use of acellular membranes as a protective material for silicone prostheses has been gaining attention due to their ability to prevent this adverse outcome. For this reason, the evaluation of the tissue-material integration and the induced biostimulation by acellular membranes results crucial. Evaluation of in vivo tissue integration and biostimulation induced by three different natural acellular collagen membranes. METHODS: Scanning electron microscopy was performed to analyse the membrane porosity and cells-biomaterial interaction in vitro, both in dry and wet conditions. Adipose-derived stem cells were cultured in the presence of membranes, and the colonisation capacity and differentiation potential of cells were assessed. In vivo tests and ex vivo analyses have been performed to evaluate dermal integration, absorption degree and biostimulation induced by the evaluated membrane. RESULTS: Analysis performed in vitro on the three different acellular dermal matrices evidenced that porosity and the morphological structure of membranes influence the liquid swelling ratio, affecting the cell mobility and the colonisation capacity. Moreover, the evaluated membranes influenced in different manner the adipose derived stem cells differentiation and their survival. In vivo investigation indicated that the absorption degree and the fluid accumulation surrounding the implant were membrane-dependent. Finally, ex vivo analysis confirmed the membrane-dependent behavior revealing different degree of tissue integration and biostimulation, such as adipogenic stimulation. CONCLUSION: The physico-chemical characteristics of the membranes play a key role in the biostimulation of the cellular environment inducing the development of well-organized adipose tissue.
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Implante Mamário , Implantes de Mama , Implante Mamário/efeitos adversos , Implante Mamário/métodos , Implantes de Mama/efeitos adversos , Colágeno , Seguimentos , Mastectomia , Estudos Retrospectivos , SiliconesRESUMO
BACKGROUND: Breast reconstruction plays a central role in the outcome management of patients with breast cancer, particularly in terms of quality of life (QoL), which must be weighed carefully when considering the available surgical options. In the context of implant-based breast reconstruction, immediate replacement with prosthesis (direct-to-implant (DTI)) and acellular dermal matrix (ADM) is gaining popularity, at the expense of the traditional two-stage implant-based breast reconstruction with tissue expander (TE), and the literature suggests that patients tend to prefer interventions with "immediate" therapeutic efficacy and aesthetic satisfaction that obviate the need for further invasive surgery. We investigated this hypothesis by administering the BREAST-Q™ questionnaire to two groups of patients who had undergone the respective procedures. METHODS: We performed a cross-sectional observational study of 192 consecutive mastectomy patients who received implant-based reconstruction, comparing health-related quality of life (HR-QoL), patient-related outcomes (PROs) and satisfaction in patients who had undergone immediate dual plane DTI with ADM (96) versus the two-stage submuscular approach (96). We also counted the number of surgeries required in each group to achieve a definitive outcome. FINDINGS: Our study revealed no major differences in terms of QoL scores, with the two approaches being largely comparable. However, single-stage reconstruction seems to offer the additional advantages of better satisfaction with the care received, sparing the patient temporary body image dissatisfaction and reducing the number of surgeries required, thereby lessening the burden on the patient, the healthcare system and society as a whole.
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Implante Mamário , Neoplasias da Mama , Mamoplastia , Mastectomia , Qualidade de Vida , Expansão de Tecido , Insatisfação Corporal/psicologia , Implante Mamário/instrumentação , Implante Mamário/métodos , Implante Mamário/psicologia , Implantes de Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Estudos Transversais , Estética , Feminino , Humanos , Itália/epidemiologia , Mamoplastia/instrumentação , Mamoplastia/métodos , Mamoplastia/psicologia , Mamoplastia/reabilitação , Mastectomia/efeitos adversos , Mastectomia/métodos , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Satisfação do Paciente , Expansão de Tecido/instrumentação , Expansão de Tecido/métodos , Expansão de Tecido/psicologia , Dispositivos para Expansão de Tecidos , Resultado do TratamentoRESUMO
OBJECTIVE: To summarize available evidence on clitoral reconstruction after Female genital mutilations/cut (FGM/C). STUDY DESIGN: Systematic review of the literature to identify studies on clitoral reconstruction after previous FGM/C with at least 6 months of follow-up. The literature search was performed in the following databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. The period considered was from the database inception to June 30th, 2020. MAIN OUTCOME MEASURES: Post-operative vulvar pain or dyspareunia, changes in sexual activity or orgasm, and the impact on self-image. RESULTS: We identified 8 studies; four used the same "Foldès technique", and four adopted similar techniques based on the downward mobilization of the clitoral stump, with different reconstructions of glans and prepuce. The postoperative complication rate was reported at 5.3%. Sexual function is the only outcome investigated by all studies, which consistently suggest that clitoral reconstruction appear effective to improve clitoral pleasure/orgasm. Almost all studies assessed self-image, which appears improved. Only 2 studies provided data about pain and/or dyspareunia, which were improved by clitoral reconstruction. However, the risk of bias is high. Most patients were lost at follow-up, and validated instruments to assess outcomes were used only in a minority of studies. CONCLUSIONS: Although clitoral reconstructive surgery for FGM/C appears safe and effective, caution is required to interpret available evidence due to significant limitations. Further studies are required to compare the proposed techniques and to confirm the effectiveness in terms of vulvar pain and/or dyspareunia, sexual activity and/or orgasm, and self-image improvement.
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Circuncisão Feminina , Procedimentos de Cirurgia Plástica , Clitóris/cirurgia , Feminino , Humanos , Orgasmo , Comportamento SexualRESUMO
The purpose of this study was to investigate the morphology of the superficial musculoaponeurotic system (SMAS). Eight embalmed cadavers were analyzed: one side of the face was macroscopically dissected; on the other side, full-thickness samples of the parotid, zygomatic, nasolabial fold and buccal regions were taken. In all specimens, a laminar connective tissue layer (SMAS) bounding two different fibroadipose connective layers was identified. The superficial fibroadipose layer presented vertically oriented fibrous septa, connecting the dermis with the superficial aspect of the SMAS. In the deep fibroadipose connective layer, the fibrous septa were obliquely oriented, connecting the deep aspect of the SMAS to the parotid-masseteric fascia. This basic arrangement shows progressive thinning of the SMAS from the preauricular district to the nasolabial fold (p < 0.05). In the parotid region, the mean thicknesses of the superficial and deep fibroadipose connective tissues were 1.63 and 0.8 mm, respectively, whereas in the region of the nasolabial fold the superficial layer is not recognizable and the mean thickness of the deep fibroadipose connective layer was 2.9 mm. The connective subcutaneous tissue of the face forms a three-dimensional network connecting the SMAS to the dermis and deep muscles. These connective laminae connect adipose lobules of various sizes within the superficial and deep fibroadipose tissues, creating a three-dimensional network which modulates transmission of muscle contractions to the skin. Changes in the quantitative and qualitative characteristics of the fibroadipose connective system, reducing its viscoelastic properties, may contribute to ptosis of facial soft tissues during aging.
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Bochecha , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/citologia , Envelhecimento , Bochecha/anatomia & histologia , Bochecha/patologia , Células do Tecido Conjuntivo/citologia , Derme/anatomia & histologia , Derme/citologia , Músculos Faciais/anatomia & histologia , Músculos Faciais/citologia , Humanos , Região Parotídea/anatomia & histologia , Tela Subcutânea/anatomia & histologiaRESUMO
BACKGROUND/AIMS: The aim of this study was to analyse the relationships between the expansions of the pectoral girdle muscles, i.e. pectoralis major, latissimus dorsi and deltoid, and the brachial fascia. METHODS: Thirty shoulder specimens from 15 unembalmed adult cadavers were studied by dissection and in vivo radiological studies were performed in 20 patients using magnetic resonance (MR) imaging. RESULTS: The clavicular part of the pectoralis major muscle sent a fibrous expansion onto the anterior portion of the brachial fascia, its costal part onto the medial portion and medial intermuscular septum. The latissimus dorsi muscle showed a triangular fibrous expansion onto the posterior portion of the brachial fascia. The posterior part of the deltoid muscle inserted muscular fibres directly onto the posterior portion of the brachial fascia, its lateral part onto the lateral portion and the lateral intermuscular septum. In MR images, the brachial fascia appeared as a low-signal-intensity sinuous line of connective tissue, sharply delineated in T(1)-weighted sequences. CONCLUSION: The expansions of the pectoral girdle muscles onto the brachial fascia were present in all the subjects and showed a quite constant course with a specific spatial organization. During the various movements of the arm, these expansions stretch selective portions of the brachial fascia, with possible activation of specific patterns of fascial proprioceptors.
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Fáscia/anatomia & histologia , Músculos Peitorais/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Dissecação , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
The longitudinal anal muscle (LAM) has been described as a vertical layer of muscular tissue interposed between the circular layers of the internal (IAS) and external (EAS) anal sphincters. There is, however, no general agreement in the literature on its composition and attachments. The aim of this study was to investigate the histological structure, attachments, and topography of the LAM in order to evaluate its role in continence and defecation, thus enhancing knowledge of the surgical anatomy of this region. After in situ formalin fixation, the pelvic viscera were removed from eight male and eight female cadavers (age range: 52-72 years). Serial macrosections of the bladder base, lower rectum and anal canal, cervix and pelvic floor complex, cut in the transverse (six specimens) and coronal (six specimens) planes, underwent histological and immunohistochemical studies. Four specimens were studied using the E12 sheet plastination technique. The LAM was identified in 10/12 specimens (83%). Transverse and coronal sections made clear that it is a longitudinal layer of muscular tissue, marking the boundary between the internal and external anal sphincters. From the anorectal junction it extends along the anal canal, receives fibers from the innermost part of the puborectalis and the puboanalis muscles, and terminates with seven to nine fibro-elastic septa, which traverse the subcutaneous part of the external anal sphincter, reaching the perianal dermis. In the transverse plane, the mean thickness of the LAM was 1.68 +/- 0.27 mm. Immunohistochemical staining showed that the LAM consists of predominantly outer striated muscle fibers and smaller numbers of inner smooth muscle fibers, respectively coming from the levator ani muscle and from the longitudinal muscular layer of the rectum. The oblique fibers suggest that the LAM may represent the intermediate longitudinal course of small bridging muscle bundles going reciprocally from the striated EAS to the smooth IAS and vice versa. The spatial result is the helical course of striated and smooth muscle fibers between the EAS and IAS, which contribute not only to the narrowing but also to some shortening of the anal canal during sphincter contraction. Thus, rather than being a boundary, the LAM gives anatomical evidence of a functional connection between two muscle systems with different structures and topography.
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Canal Anal/citologia , Músculo Esquelético/citologia , Músculo Liso/citologia , Idoso , Canal Anal/anatomia & histologia , Canal Anal/fisiologia , Defecação/fisiologia , Incontinência Fecal/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Músculo Liso/fisiologiaRESUMO
UNLABELLED: Skin-reduction mastectomy with prepectoral implant reconstruction is a novel technique for immediate breast reconstruction, with subcutaneous implant placement in patients eligible for skin-reducing mastectomy. Implants were placed above the pectoralis muscles in a compound pocket made by a dermal flap and acellular dermal matrix. The procedure was performed on 33 breasts in 27 selected patients. In three cases, there was skin ischemia; in one case, it healed spontaneously; and in two patients, a surgical necrosectomy and primary closure were needed. No implant loss occurred. This new technique proved to be a useful alternative, with good cosmetic results, in selected patients requiring mastectomy. These preliminary results need to be confirmed by long-term and comparative studies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
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Implantes de Mama , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia/métodos , Músculos Peitorais/transplante , Retalhos Cirúrgicos , Derme Acelular , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Mamilos/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The acellular dermal matrix (ADM)-assisted breast reconstruction technique is widely known, but discouraging results due to early postoperative complications have been reported. As the literature identifies seroma as the most common issue after breast surgery without identifying its pathogenesis, we aimed to report the trend of postoperative daily serum collection after ADM-assisted breast reconstruction and compare it with data in the literature in order to discover more about this little-known topic. METHODS: A retrospective study on 28 consecutive patients who received ADM-assisted breast reconstruction between February 2013 and February 2014 was performed. In order to reduce the number of variables that could affect serum production, only one brand of ADM was used and all tissues were handled gently and precisely. The daily drainage volume was recorded per patient during the first four days of hospitalization. Likewise, postoperative complications were noted during routine follow-up. RESULTS: In total, five (17.9%) bilateral and 23 (82.1%) unilateral ADM-assisted breast reconstructions (33 implants) were performed. The mean age, body mass index, and length of hospital stay were 53.6 years, 21.3 kg/m(2), and 4.5 days, respectively. One major complication led to implant loss (3.0%), and nine minor complications were successfully treated with ambulatory surgery (27.3%). Serum collection linearly decreased after 24 hours postoperatively. CONCLUSIONS: Daily drainage decreased following the theoretical decline of acute inflammation. In concordance with the literature, daily serum production may not be related to the use of ADM.
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Many genetic alterations, including predisposing or somatic mutations, may contribute toward the development of melanoma. Although CDKN2A and CDK4 are high-penetrance genes for melanoma, MC1R is a low-penetrance gene that has been associated most consistently with the disease. Moreover, BRAF is the most frequently somatically altered oncogene and is a validated therapeutic target in melanoma. This paper reports a case of multiple primary melanoma with germline CDK4 mutation, MC1R variant, and somatic BRAF mutation in nine out of 10 melanomas, indicating that a common pathogenesis, because of a predisposing genetic background, may be shared among distinct subsequent melanomas of probable clonal origin. After 3 months of targeted therapy with BRAF inhibitor, our patient developed resistance with rapid progression of the disease leading to death. This is the first case in which early resistance to BRAF inhibitor has been reported in a patient with CDK4 germline mutation.
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Quinase 4 Dependente de Ciclina/genética , Mutação em Linhagem Germinativa , Melanoma/genética , Neoplasias Primárias Múltiplas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Adulto , Resistencia a Medicamentos Antineoplásicos/genética , Evolução Fatal , Predisposição Genética para Doença , Humanos , Indóis/uso terapêutico , Masculino , Melanoma/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/uso terapêutico , VemurafenibRESUMO
BACKGROUND: Platelet preparations for tissue healing are usually preactivated before application to deliver concentrated growth factors. In this study, the authors investigated the differences between nonactivated and thrombin-activated platelets in wound healing. METHODS: The healing effects (i.e., wound closure, myofibroblast formation, and angiogenesis) of nonactivated and thrombin-activated platelets were compared in experimental wounds in diabetic (db/db) animals. In vitro, fibroblast phenotype and function were tested in response to platelets and activated platelets. No treatment served as a negative control. RESULTS: Wounds treated with platelets reached 90 percent closure after 15 days, faster than activated platelets (26 days), and with higher levels of myofibroblasts and angiogenesis. In vitro, platelets enhanced cell migration and induced two-fold higher myofibroblast differentiation and contraction compared with activated platelets. CONCLUSIONS: Platelets stimulate wound healing more efficiently compared with activated platelets by enhancing fibroblast differentiation and contractile function. Similar levels of growth factors may induce different biological effects when delivered "on demand" rather than in an initial bolus.
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Terapia Baseada em Transplante de Células e Tecidos/métodos , Diabetes Mellitus Experimental/fisiopatologia , Fibroblastos/fisiologia , Ativação Plaquetária/fisiologia , Plasma Rico em Plaquetas/fisiologia , Cicatrização/fisiologia , Animais , Diferenciação Celular , Movimento Celular/fisiologia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/fisiologia , Neovascularização Fisiológica , Trombina/metabolismoRESUMO
BACKGROUND: The use of glycerol and subsequent research enabling the conservation of tissues over time have led to the establishment and development of tissue banks, first in the USA and then in Europe. The Verona Tissue Bank was instituted in 2003 as the Regional Centre for the storage of skin and bone, adding to the already existing Italian banks at Turin, Milan, Cesena and Siena. This retrospective study analyses the use of banked skin (autologous and allogeneic grafts) from April 2003 (date of starting activity) to December 2007, in 171 patients with burns and four with necrotising fasciitis at the Burns Centre of Verona. MATERIALS AND METHODS: Homologous skin was used for superficial and deep skin burns to protect the residual structures, thus facilitating healing by spontaneous re-epithelialisation, and for deep burns after eschar removal to clean and prepare the base of the lesion for the definitive autologous graft. The placement of a homologous graft alone led to spontaneous healing of lesions in 65 patients (36 aged >15 years and 29 aged <15 years) with superficial skin burns, while the remaining 106 patients (84 aged >15 years and 22 aged <15 years) with deeper burns underwent surgery. CONCLUSIONS: The results obtained confirm the essential role of banked skin in covering superficial burns in order to protect important underlying structures and in deep burns by guaranteeing a good preparation of the base of the lesion for the subsequent definitive autologous graft.
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Queimaduras/cirurgia , Criopreservação , Transplante de Pele , Bancos de Tecidos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante HomólogoRESUMO
Ischemic wounds are characterized by oxygen levels lower than that of healthy skin (hypoxia) and poor healing. To better understand the pathophysiology of impaired wound healing, we investigated how switching from high (21%) to low (2%) oxygen levels directly affects cultured skin myofibroblasts, essential cells for the normal wound repair process. Myofibroblast differentiation and function were assessed by quantifying α-smooth muscle actin expression and cell contraction in collagen gels and on wrinkling silicone substrates. Culture for 5 days at 2% oxygen is perceived as hypoxia and significantly reduced myofibroblast differentiation and contraction despite high levels of the profibrotic transforming growth factor-ß1. Analysis of α-smooth muscle actin expression on wrinkling substrates over time showed that reduced myofibroblast contraction preceded α-smooth muscle actin disassembly from stress fibers after switching from 21 to 2% oxygen. These effects were reversible by restoring high oxygen conditions and by applying mechanical stress. We suggest that mechanical challenge is a clinical relevant strategy to improve ischemic and chronic wound healing by supporting myofibroblast formation.
Assuntos
Fibroblastos/metabolismo , Hipóxia/patologia , Oxigênio/metabolismo , Cicatrização/fisiologia , Ferimentos e Lesões/patologia , Animais , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Células Cultivadas , Fibroblastos/citologia , Humanos , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Isquemia/metabolismo , Isquemia/patologia , Isquemia/fisiopatologia , Oxigênio/farmacologia , Ratos , Pele/lesões , Pele/metabolismo , Pele/patologia , Tela Subcutânea/fisiologia , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/fisiopatologiaRESUMO
We studied by immunocytochemistry the expression of NCAM in human carotid bodies, sampled at autopsy from 16 adult subjects (mean age +/- SD: 44.3 +/- 3.4 years). No NCAM immunoreactivity was visible in type II cells. An high percentage (78.3 +/- 7.2%) of type I cells showed positive anti-NCAM immunoreaction. Statistically significant differences were not found in anti-NCAM immunostaining of light and dark cells (80.2 +/- 6.2% vs 74.7 +/- 13.4%, P>0.05). The high expression level of NCAM in the carotid body indicates a role in regulating adhesion between type I cells. The ascertained role of NCAM in neural mechanisms of differentiation, survival and cell plasticity suggests a possible involvement in the development/differentiation process of the carotid body and in determining cellular/molecular changes due to chronic hypoxia.
Assuntos
Corpo Carotídeo/metabolismo , Células Quimiorreceptoras/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Adulto , Corpo Carotídeo/citologia , Adesão Celular/fisiologia , Diferenciação Celular/fisiologia , Forma Celular/fisiologia , Células Quimiorreceptoras/classificação , Células Quimiorreceptoras/citologia , Citoplasma/metabolismo , Citoplasma/ultraestrutura , Feminino , Humanos , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Moléculas de Adesão de Célula Nervosa/análise , Plasticidade Neuronal/fisiologiaRESUMO
In the literature, few studies detailed morphometric parameters of the inferior olivary complex, and mainly applying biased methods based on counting in a two-dimensional plane. In the present work, the unbiased quantitative method of the optic disector was applied in order to analyse neuronal densities, nuclear volumes and total neuron numbers of the principal (PION), medial (MION) and dorsal (DION) nuclei of the inferior olivary complex in adults (16 male, 6 female; mean age: 37 years) and infants (5 male, 5 female; mean age: 5 months). In both adult and infant series, statistically significant differences were not found in neuronal densities between the various inferior olivary nuclei. All the nuclei showed higher volumes and lower neuronal densities in adults than infants, without statistically significant differences in total neuron numbers, thus suggesting postnatal development of the neuropil.