Aesthetic medicine represents an emerging field for many specialties. Nowadays, a plethora of approaches are available to rejuvenate the human body and face, the latter being a frequent target for the placement of filling substances to correct wrinkles and volume loss. Nevertheless, based on the many products on the market, treating clinicians must pay specific attention to the properties of the respective materials, their associated side effects and any specific handling requirements to prevent potential short- and long-term adverse events.
Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients, and are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Both entities have different clinical and histochemical characteristics, and unfortunately still represent a great challenge for clinicians due to lack of efficacious treatments. Current advances in molecular biology and genetics reveal new preventive and therapeutical options which represent a hope to manage this highly prevalent, chronic and disabling problem, with long-term beneficial outcomes and improvement of quality of life. While we wait for these translational clinical products to be marketed, however, it is imperative to know the basics of the currently existing wide array of strategies to deal with excessive scars: from the classical corticotherapy, to the most recent botulinum toxin and lasers. The main aim of this review paper is to offer a useful up-to-date guideline to prevent and treat keloids and hypertrophic scars.
Keloids and hypertrophic scars are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research have contributed to unravel new bench-to-bedside scar therapies and to dissect the complex signalling pathways involved. Peptides such as the transforming growth factor beta (TGF-?) superfamily, with Smads, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-?4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scars. The aim of this review is to describe the basic complexity of these new molecular scar management strategies and point out new fibrosis research lines.
Striae distensae (SD) represent a common disfiguring cutaneous condition characterized by linear reddish smooth bands of atrophic-appearing skin. Most often SD develop in areas of dermal damage produced by stretching. Numerous treatment modalities have been applied with varying success. Novel approaches include treatments with various types of lasers with the flashlamp-pumped pulsed dye laser (PDL; 585 nm) being the most commonly reported. Very recently, fractional photothermolysis has been suggested as an effective method for the treatment of SD. Here, we report on the effect of an ablative Erbium:YAG fractional laser in two cases of axillary SD in comparison with a 585-nm PDL.
In the context of growing aesthetic awareness, a rising number of patients feel disappointed with their scars and are frequently seeking help for functional and aesthetic improvement. However, excessive scarring following surgery or trauma remains difficult to improve despite a plethora of advocated treatment strategies as frequently observed in daily clinical routine. It is thus still preferable to prevent scarring by minimizing risk factors as much as possible. Hence, it remains crucial for the physician to be aware of basic knowledge of healing mechanisms and skin anatomy, as well as an appreciation of suture material and wound closure techniques to minimize the risk of postoperative scarring. Next to existing, well known prophylactic and therapeutic strategies for the improvement of excessive scarring, this article discusses emerging techniques such as intralesional cryotherapy, intralesional 5-fluorouracil, interferon, and bleomycin. Some of them have been successfully tested in well-designed trials and already have extended or may extend the current spectrum of excessive scar treatment in the near future. Innovative options such as imiquimod 5% cream, photodynamic therapy, or botulinum toxin A may also be of certain importance; however, the data currently available is too contradictory for definite recommendations.
Due to its strong water-binding potential, hyaluronic acid (HA) is a well-known active ingredient for cosmetic applications. Native HA is proposed to help the skin to retain and maintain elasticity, turgor and moisture.
In current medical practice, wound therapy remains a clinical challenge and much effort has been focused on the development of novel therapeutic approaches for wound treatment. Gene therapy, initially developed for treatment of congenital defects, represents a promising option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines have shown the most potential. The majority of gene delivery systems are based on viral transfection, naked DNA application, high pressure injection, and liposomal vectors. Besides advances stemming from breakthroughs in recombinant growth factors and bioengineered skin, there has been a significant increase in the understanding of stem cell biology in the field of cutaneous wound healing. A variety of sources, such as bone marrow, umbilical cord blood, adipose tissue and skin/hair follicles, have been utilized to isolate stem cells and to modulate the healing response of acute and chronic wounds. Recent data have demonstrated the feasibility of autologous adult stem cell therapy in cutaneous repair and regeneration. Very recently, stem cell based skin engineering in conjunction with gene recombination, in which the stem cells act as both the seed cells and the vehicle for gene delivery to the wound site, represents the most attractive field for generating a regenerative strategy for wound therapy. The aim of this article is to discuss the use and the potential of these novel technologies in order to improve wound healing capacities.
The hypermetabolic response in critically ill patients is characterized by hyperdynamic circulatory, physiologic, catabolic and immune system responses. Failure to satisfy overwhelming energy and protein requirements after, and during critical illness, results in multiorgan dysfunction, increased susceptibility to infection, and death. Attenuation of the hypermetabolic response by various pharmacologic modalities is emerging as an essential component of the management of severe burn patients. This review focuses on the more recent advances in therapeutic strategies to attenuate the hypermetabolic response and its associated insulin resistance postburn.
Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions.
Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes.
Excessive scars form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patients quality of life, both physically and psychologically. Multiple studies on hypertrophic scar and keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction. In this review we summarize the current understanding of the pathophysiology underlying keloid and hypertrophic scar formation and discuss established treatments and novel therapeutic strategies.
Human immunodeficiency virus (HIV)-associated facial lipoatrophy (FLA) represents a common and highly stigmatizing side effect of retroviral therapy. By causing loss of subcutaneous adipose tissue mainly in the cheek, temple and periocular area, FLA can significantly affect the patients quality of life, both physically and psychologically. A limited quantity of data has been published on various filling substances for the management of FLA. Here, the authors present two patients with HIV-associated FLA successfully treated with a novel HA filler over a period of 24 months.
Insulin resistance with its associated hyperglycemias represents one significant contributor to mortality in burned patients. A variety of cellular stress-signaling pathways are activated as a consequence of burn. A key player in the cellular stress response is the endoplasmic reticulum (ER). Here, we investigated a possible role for ER-stress pathways in the progression of insulin function dysregulation postburn. Rats received a 60% total body surface area thermal injury, and a laparotomy was performed at 24, 72, and 192 h postburn. Liver was harvested before and 1 min after insulin injection (1 IU/kg) into the portal vein, and expression patterns of various proteins known to be involved in insulin and ER-stress signaling were determined by Western blotting. mRNA expression of glucose-6-phosphatase and glucokinase were determined by reverse-transcriptase-polymerase chain reaction and fasting serum glucose and insulin levels by standard enzymatic and enzyme-linked immunosorbent assay techniques, respectively. Insulin resistance indicated by increased glucose and insulin levels occurred starting 24 h postburn. Burn injury resulted in activation of ER stress pathways, reflected by significantly increased accumulation of phospho-PKR-like ER-kinase and phosphorylated inositol requiring enzyme 1, leading to an elevation of phospho-c-Jun N-terminal kinase and serine phosphorylation of insulin receptor substrate (IRS) 1 postburn. Insulin administration caused a significant increase in tyrosine phosphorylation of IRS-1, leading to activation of the phosphatidylinositol 3 kinase/Akt pathway in normal liver. Postburn tyrosine phosphorylation of IRS-1 was significantly impaired, associated with an inactivation of signaling molecules acting downstream of IRS-1, leading to significantly elevated transcription of glucose-6-phosphatase and significantly decreased mRNA expression of glucokinase. Activation of ER-stress signaling cascades may explain metabolic abnormalities involving insulin action after burn.
Different therapies that effect wound repair have been proposed over the last few decades. This article reviews the emerging fields of gene and stem cell therapy in wound healing. Gene therapy, initially developed for treatment of congenital defects, is a new option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines showed the greatest potential. The majority of gene delivery systems are based on viral transfection, naked DNA application, high pressure injection, or liposomal vectors. Embryonic and adult stem cells have a prolonged self-renewal capacity with the ability to differentiate into various tissue types. A variety of sources, such as bone marrow, peripheral blood, umbilical cord blood, adipose tissue, skin and hair follicles, have been utilized to isolate stem cells to accelerate the healing response of acute and chronic wounds. Recently, the combination of gene and stem cell therapy has emerged as a promising approach for treatment of chronic and acute wounds.
A hallmark of the disease state following severe burn injury is decreased liver function, which results in gross metabolic derangements that compromise patient survival. The underlying mechanisms leading to hepatocyte dysfunction after burn are essentially unknown. The aim of the present study was to determine the underlying mechanisms leading to hepatocyte dysfunction and apoptosis after burn. Rats were randomized to either control (no burn) or burn (60% total body surface area burn) and sacrificed at various time-points. Liver was either perfused to isolate primary rat hepatocytes, which were used for in vitro calcium imaging, or liver was harvested and processed for immunohistology, transmission electron microscopy, mitochondrial isolation, mass spectroscopy or Western blotting to determine the hepatic response to burn injury in vivo. We found that thermal injury leads to severely depleted endoplasmic reticulum (ER) calcium stores and consequent elevated cytosolic calcium concentrations in primary hepatocytes in vitro. Burn-induced ER calcium depletion caused depressed hepatocyte responsiveness to signalling molecules that regulate hepatic homeostasis, such as vasopressin and the purinergic agonist ATP. In vivo, thermal injury resulted in activation of the ER stress response and major alterations in mitochondrial structure and function - effects which may be mediated by increased calcium release by inositol 1,4,5-trisphosphate receptors. Our results reveal that thermal injury leads to dramatic hepatic disturbances in calcium homeostasis and resultant ER stress leading to mitochondrial abnormalities contributing to hepatic dysfunction and apoptosis after burn injury.
In addition to forming the epithelial barrier against the outside environment keratinocytes are immunologically active cells. In the treatment of severely burned skin, cryoconserved keratinocyte allografts gain in importance. It has been proposed that these allografts accelerate wound healing also due to the expression of a favourable--keratinocyte-derived--cytokine and growth factor milieu.
We determined whether postburn hyperglycemia and insulin resistance are associated with endoplasmic reticulum (ER) stress/unfolded protein response (UPR) activation leading to impaired insulin receptor signaling.
OBJECTIVE:: To evaluate whether a panel of common biomedical markers can be utilized as trajectories to determine survival in pediatric burn patients. BACKGROUND:: Despite major advances in clinical care, of the more than 1 million people burned in the United States each year, more than 4500 die as a result of their burn injuries. The ability to predict patient outcome or anticipate clinical trajectories using plasma protein expression would allow personalization of clinical care to optimize the potential for patient survival. METHODS:: A total of 230 severely burned children with burns exceeding 30% of the total body surface, requiring at least 1 surgical procedure were enrolled in this prospective cohort study. Demographics, clinical outcomes, and inflammatory and acute-phase responses (serum cytokines, hormones, and proteins) were determined at admission and at 11 time points for up to 180 days postburn. Statistical analysis was performed using a 1-way analysis of variance, the Student t test, ? test, and Mann-Whitney test where appropriate. RESULTS:: Survivors and nonsurvivors exhibited profound differences in critical markers of inflammation and metabolism at each time point. Nonsurvivors had significantly higher serum levels of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, C-reactive protein, glucose, insulin, blood urea nitrogen, creatinine, and bilirubin (P < 0.05). Furthermore, nonsurvivors exhibited a vastly increased hypermetabolic response that was associated with increases in organ dysfunction and sepsis when compared with survivors (P < 0.05). CONCLUSIONS:: Nonsurvivors have different trajectories in inflammatory, metabolic, and acute phase responses allowing differentiation of nonsurvivors from survivors and now possibly allowing novel predictive models to improve and personalize burn outcomes.
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