Cesar Isaac

Short-term effects of 7-ketocholesterol on human adipose tissue mesenchymal stem cells in vitro.

Oxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and non-enzymatic oxidation. Among them, 7-ketocholesterol (7-KC) is one of the most important. It has potent effects in cell death processes, including cytoxicity and apoptosis induction. Mesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Very little is known about the effects of oxysterols in MSCs. Here, we describe the short-term cytotoxic effect of 7-ketocholesterol on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from two young, healthy women. After 24 h incubation with 7-KC, mitochondrial hyperpolarization was observed, followed by a slight increase in the level of apoptosis and changes in actin organization. Finally, the IC50 of 7-KC was higher in these cells than has been observed or described in other normal or cancer cell lines.

Substitutos cutâneos: conceitos atuais e proposta de classificação

Complex wounds are characterized by complete loss of cutaneous cover. The most common plastic surgery technique is the autogenous skin graft; however, the amount of material available from donor areas is often limited. The development of synthetic or biological products as skin substitutes is therefore an area of interest. The present study aimed to classify the different types of skin substitutes available based on three criteria: the skin layer to be replaced, which can be categorized into epidermal (E), dermal (D), and dermal-epidermal composites (C); the durability in the wound bed, which can be temporary (T) or permanent (P); and the origin of the material, subdivided into biological (b), biosynthetic (bs), and synthetic (s).

Pentoxifylline modifies three-dimensional collagen lattice model contraction and expression of collagen types I and III by human fibroblasts derived from post-burn hypertrophic scars and from normal skin

Fibroblasts are thought to be partially responsible for the persisting contractile forces that result in burn contractures. Using a monolayer cell culture and fibroblast populated collagen lattice (FPCL) three-dimensional model we subjected hypertrophic scar and non-cicatricial fibroblasts to the antifibrogenic agent pentoxifylline (PTF - 1mg/mL) in order to reduce proliferation, collagen types I and III synthesis and model contraction. Fibroblasts were isolated from post-burn hypertrophic scars (HSHF) and non-scarred skin (NHF). Cells were grown in monolayers or incorporated into FPCLs and exposed to PTF. In monolayer, cell number proliferation was reduced (46.35% in HSHF group and 37.73% in NHF group, p<0.0001). PTF selectively inhibited collagen III synthesis in the HSHF group while inhibition was more evident to type I collagen synthesis in the NHF group. PTF also reduced contraction in both (HSHF and NHF) FPCL.

Clinical trial comparing 3 different wound dressings for the management of partial-thickness skin graft donor sites.

PURPOSE: A review of the literature reveals a lack of consensus regarding local management of skin graft donor sites. This study was undertaken to determine the effects of 3 different dressings on healing of donor sites and patient discomfort related to donor sites. DESIGN: This study is a comparison cohort study. SUBJECTS AND SETTING: We recruited 34 burn patients scheduled for partial-thickness skin grafts; their mean age was 36 ± 18 years (mean ± SD, range 20 to 54 years), and 63% were male. All subjects were managed at Burn Unity Care, located in Sao Paulo, Brazil. MATERIALS AND METHODS: Subjects were randomly allocated to 1 of 3 groups: (1) a study group (group A) whose donor sites were dressed with a bovine collagen calcium-alginate dressing covered with transparent polyurethane film; (2) a second intervention group (group B), whose donor sites were dressed only with transparent polyurethane film dressing; and (3) a control group whose donor sites were dressed with rayon soaked in 0.9% saline (group C). Two independent observers assessed donor site wounds for epithelialization, scabbing, quantity and characteristics of exudate, and complications. Pain was measured using the visual analog scale, the brief pain inventory, and Index of Pain Management. RESULTS: Subjects managed with the bovine collagen calcium-alginate dressing covered with transparent polyurethane film (group A) achieved the greatest epithelialization (6.3 vs 8.2 for thin film dressing only P < .02 and 6.3 vs 11.7 days for control group P < .01). Patients managed with the bovine collagen calcium-alginate dressing covered with transparent polyurethane film also reported less pain that subjects allocated to the control (group C) or thin film only group (group B), (P < .05). Ninety percent of subjects allocated to the calcium alginate covered with thin film dressing reported mild pain intensity on the Visual Analog Scale, 85% of did not report pain localized to the donor site on the brief pain inventory, and scores on the Index of Pain Management ranged from 23 to 11. CONCLUSION: Study findings suggest that use of a collagen calcium-alginate dressing with a transparent film covering reduces the time for complete epithelialization and may reduce pain related to skin graft donor sites.

Intralesional pentoxifylline as an adjuvant treatment for perioral post-burn hypertrophic scars

Pentoxifylline (PTF), a methylxanthine derivative, has therapeutic use as an antifibrotic agent. In vitro, PTF inhibits the production of collagen and reduces the proliferation of fibroblasts in hypertrophic scars. This study aimed to evaluate changes in the elasticity of hypertrophic scars in the peribuccal area in burned patients, who presented with mouth-opening limitation. Eighteen patients were divided into two groups. The case group (n=10) was treated with PTF 1 mg ml(-1), while in the control group (n=8) no treatment was performed. Measurements of mouth opening (lip-to-lip and tooth-to-tooth distances in mm) were taken, before and after five therapeutic sessions with pentoxifylline with weekly intervals. The variations of these measures (Delta%) were calculated and submitted to statistical analyses. There was a significant improvement in the opening of the mouth, in vermilion distance (V=3.20 mm) as much as the dental distance (DD=4.19 mm) in the treated group, than in the control group. It was noted that pentoxifylline increases the elasticity of hypertrophic scars in the perioral area.

Comparisons of the results of peripheral nerve defect repair with fibrin conduit and autologous nerve graft: An experimental study in rats

The standard treatment for nerve defects is nerve autograft. There is no conduit available that provides the same regenerative capacity of nerve autograft. This study evaluated the histological and functional recovery of nerve defects treated with fibrin conduit in comparison to the nerve autograft, in a rat model.

Treatment of extrinsic ectropion on burned face with facial suspension technique

UNLABELLED The extrinsic ectropion is a condition with low prevalence characterized by an ectropion with normal eyelid and anatomy unchanged and the cause is found in tissues adjacent orbits. There are not many studies in the literature regarding their treatment, especially without addressing the eyelid respecting its anatomical integrity. PURPOSE To evaluate the outcome of 8 extrinsic ectropions secondary to facial burns treated with facial suspension technique. PATIENTS AND METHODS Five patients were evaluated with sequelae of facial burns and extrinsic unilateral or bilateral ectropion, a total of 8 ectropions. The technique used was the endoscopic facial suspension with or without release of the facial scar retraction. We evaluated the position of the lower lid over medium-pupillary line, symptoms, complications and patient satisfaction in a 24 months follow-up. RESULTS 6 Peri-orbital regions showed good results and two moderate results, all cases had clinical improvement of the ectropion, the symptoms and the esthetic aspect; there was not any complication or reoperation. There was a gain of 2.2-26.2% of the lower eyelid margin position in relation to the horizontal mid-pupillary line. CONCLUSION The endoscopic facial suspension proved to be a surgical technique with low morbidity and efficient treatment in 8 facial extrinsic ectropion.

Oxysterols in adipose tissue-derived mesenchymal stem cell proliferation and death.

Mesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Oxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and non-enzymatic oxidation. Potent effects in cell death processes, including cytoxicity and apoptosis induction, were described in several cell lines. Very little is known about the effects of oxysterols in MSCs. 7-ketocholesterol (7-KC), one of the most important oxysterols, was shown to be cytotoxic to human adipose tissue-derived MSCs. Here, we describe the short-term (24h) cytotoxic effects of cholestan-3α-5β-6α-triol, 3,5 cholestan-7-one, (3α-5β-6α)- cholestane-3,6-diol, 7-oxocholest-5-en-3β-yl acetate, and 5β-6β epoxy-cholesterol, on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from three young, healthy women. Oxysterols, with the exception of 3,5 cholestan-7-one and 7-oxocholest-5-en-3β-yl acetate, led to a complex mode of cell death that include apoptosis, necrosis and autophagy, depending on the type of oxysterol and concentration, being cholestan-3α-5β-6α-triol the most effective. Inhibition of proliferation was also promoted by these oxysterols, but no changes in cell cycle were observed.

Sistematização de curativos para o tratamento clínico das feridas

The treatment of cutaneous wounds includes both medical and surgical methods; dressing is one of the most commonly used clinical treatments. An extensive therapeutic toolkit comprising passive dressings or dressings with active principles can help repair wounds in various situations. Dressings are used to improve the conditions of the wound bed and may occasionally be considered the definitive treatment, whereas in some cases, they may be considered an intermediate step to surgical treatment. Intelligent and biological wound dressings are currently classified as dermal substitutes and will not be discussed in this article. Dressings should be selected on the basis of knowledge of the pathophysiology of wound healing and tissue repair while keeping the systemic problems of the patient in mind.

Role of keratinocytes in wound contraction: an impact assessment using a model of collagen matrix populated with fibroblasts

BACKGROUND: The possible participation of keratinocytes in wound remodeling has been widely studied. This study investigated the impact of keratinocytes in wound contraction. METHODS: Murine type I collagen gels populated by human fibroblasts and seeded with human keratinocytes on the surface to form a dermo-epidermal equivalent were used as the study group. Collagen gels populated by only fibroblasts were used as the control group. The criteria for the preparation and storage of gels were similar for both groups. RESULTS: An evident and statistically significant increase in gel contraction was observed in samples populated by keratinocytes compared to the control group. CONCLUSIONS: These results suggest that keratinocytes not only modulate fibroblast proliferation but also play an active role in wound contraction per se. Further research on the mechanisms involved in the communication pathways between cells and between cells and the matrix shall be assessed from the perspective of keratinocyte participation in wound healing and pathologic scarring.