Translational application of human keratinocyte-fibroblast cell sheets for accelerated wound healing in a clinically relevant type 2 diabetic rat model.

BACKGROUND AIMS: Despite advancements in wound care, wound healing remains a challenge, especially in individuals with type 2 diabetes. Cell sheet technology has emerged as an efficient and promising therapy for tissue regeneration and wound repair. Among these, bilayered human keratinocyte-fibroblast cell sheets constructed using temperature-responsive culture surfaces have been shown to mimic a normal tissue-like structure and secrete essential cytokines and growth factors that regulate the wound healing process. METHODS: This study aimed to evaluate the safety and therapeutic potential of human skin cell sheets to treat full-thickness skin defects in a rat model of type 2 diabetes. RESULTS: Our findings demonstrate that diabetic wounds transplanted with bilayered cell sheets resulted in accelerated re-epithelialization, increased angiogenesis, enhanced macrophage polarization and regeneration of tissue that closely resembled healthy skin. In contrast, the control group that did not receive cell sheet transplantation presented characteristic symptoms of impaired and delayed wound healing associated with type 2 diabetes. CONCLUSIONS: The secretory cytokines and the upregulation of Nrf2 expression in response to cell sheet transplantation are believed to have played a key role in the improved wound healing observed in diabetic rats. Our study suggests that human keratinocyte-fibroblast cell sheets hold great potential as a therapeutic alternative for diabetic ulcers.

Expansion of fibroblast cell sheets using a modified MEEK micrografting technique for wound healing applications.

Cell sheet engineering, a scaffold-free approach to fabricate functional tissue constructs from several cell monolayers, has shown promise in tissue regeneration and wound healing. Unfortunately, these cell sheets are often too small to provide sufficient wound area coverage. In this study, we describe a process to enlarge cell sheets using MEEK micrografting, a technique extensively used to expand skin autografts for large burn treatments. Human dermal fibroblast cell sheets were placed on MEEK's prefolded gauze without any use of adhesive, cut along the premarked lines and stretched out at various expansion ratios (1:3, 1:6 and 1:9), resulting in regular distribution of many square islands of fibroblasts at a much larger surface area. The cellular processes essential for wound healing, including reattachment, proliferation, and migration, of the fibroblasts on expanded MEEK gauze were superior to those on nylon dressing which served as a control. The optimal expansion ratio with the highest migration rate was 1:6, possibly due to the activation of chemical signals caused by mechanical stretching and an effective intercellular communication distance. Therefore, the combination of cell sheet engineering with the MEEK micrografting technique could provide high quality cells with a large coverage area, which would be particularly beneficial in wound care applications.

Characteristics and Safety Profiles of a Hydrocolloid Polyester Dressing Incorporated with Herbal Extract: In Vitro, in Vivo and Randomized Clinical Studies.

The polyester dressing containing herbal extract had been used for several years. However, some properties had not been investigated. This study examined three parts including in vitro studies, skin irritation in an animal model, and the pilot clinical study in traumatic wounds. In in vitro studies, six different wound dressings consisted of hydrocolloid polyester containing herbal extract (SI-HERB®), hydrofiber (Aquacel®), hydrocolloid polyester (Urgotul®), soft paraffin gauze (Bactigras®), foam (Mepilex®), and biocellulose (Suprasorb® X + PHMB) dressings were comparatively evaluated in physical properties including the fluid absorption, desorption, and fluid drainage ability. The skin irritation test was examined in a rabbit model using SI-HERB® as a tested group. In a clinical study, traumatic patients with leg wounds were randomly assigned to six wound dressings. The primary outcome was the pain level and the secondary outcomes were non-adherence and peri-wound reaction evaluating score. From the study, Bactigras® had the largest pore size but the total area of pore size per field of it was similar to SI-HERB®. There were no significant differences between SI-HERB®, Urgotul®, and Bactigras® in the percentage of absorption and desorption. No dermatologic effect was found in the animal study. In the irritation test on leg wounds, pain level, and peri-wound reaction in hydrocolloid polyester dressing group were significantly lower compared with Aquacel® and Bactigras®. The polyester dressing had the pain level after removal lower than before application while the Mepilex® and Suprasorb® presented that insignificantly increase the pain level. Erythema could be observed in Bactigras®, Aquacel®, and Suprasorb® but the edema scores were not different. A hydrocolloid polyester dressing containing herbal extract had good drainage ability. No skin irritation was reported. Pain scores, removal ability, and peri-wound reaction were also significantly lower with other types of wound dressings. These results suggested that this dressing be an alternative in wound treatment.

Preparation and characterization of human keratinocyte-fibroblast cell sheets constructed using PNIAM-co-AM grafted surfaces for burn wound healing.

Autologous skin grafting, the standard treatment for severe burns, is sometimes not possible due to the limited available skin surfaces for the procedure. With advances in tissue engineering, various cell-based skin substitutes have been developed to serve as skin replacements and to promote tissue regeneration and healing. In this work, we propose the use of cell sheet technology to fabricate keratinocyte-fibroblast tissue constructs from the temperature-responsive poly(N-isoproprylacrylamide-co-acrylamide) (PNIAM-co-AM) grafted surfaces for the treatment of burn wounds. The characteristics of the human keratinocyte and fibroblast cell sheets harvested using PNIAM-co-AM grafted surfaces were similar to those cell sheets detached from the commercially-available UpCellTM plates. Upon lowering the incubation temperature, confluent keratinocytes and fibroblasts could be detached as intact sheets, consisting of biologically active cells, as indicated by their high cell viability and their reattachment, migratory, and proliferative activities. A histological analysis of the stratified keratinocyte-fibroblast cell sheets revealed the evidence of cell migration and tissue reorganization to form two distinct epidermal and dermal layers, quite similar to the skin tissue's structure. In addition, the keratinocyte-fibroblast sheets could synthesize and release significant amounts of essential cytokines and growth factors involved in regulating the wound healing process, including IL-1α, IL-6, TNF-α, VEGF, and bFGF, implying the therapeutic effect of these cell sheets, which could be beneficial to accelerate tissue repair and regeneration, leading to faster wound healing.

Polyurethane-biomacromolecule combined foam dressing containing asiaticoside: fabrication, characterization and clinical efficacy for traumatic dermal wound treatment.

Polyurethane combined (PUC) foam dressings with various biomacromolecules were fabricated with the adsorption of asiaticoside and silver nanoparticles for traumatic wound treatment. Biomacromolecules had varying effects on physicochemical and mechanical properties of PU foam. With 2% incorporation, starches, high molecular weight chitosan and gelatin provided stiffer and more porous foams while carboxymethylcellulose had the highest compression strength but the lowest water vapor transmission. High water absorption was from foams with carboxymethylcellulose, alginate, hydroxypropyl methylcellulose and low molecular weight chitosan. Increasing the concentrations up to 12% had more prominent effect. However, powdery surface was noticed with poorer tensile properties that 6% incorporation was selected. FTIR spectra and DSC thermograms suggested interaction of PU formulation with biomacromolecules. EDS analysis confirmed existence of active compounds while acceptable stability was from sterilized PUC foam with alginate. On healthy volunteers, this selected foam dressing caused no skin irritation and retained moisture comparable to commercial product. In patients with traumatic dermal wounds, healing improvement with shorter wound closure time, higher reepithelialization and less pain score were from the selected foam dressing compared to standard gauze soaked with chlorhexidine. This PU-alginate combined foam dressing adsorbed with asiaticoside and silver nanoparticles proved advantages for traumatic dermal wound management.

Randomized Controlled Trial of Polyhexanide/Betaine Gel Versus Silver Sulfadiazine for Partial-Thickness Burn Treatment.

Silver sulfadiazine is commonly used in the treatment of partial-thickness burns, but it sometimes forms pseudo-eschar and delays wound healing. Polyhexanide/betaine gel, a new wound cleansing and moisturizing product, has some advantages in removing biofilm and promotes wound healing. This study was designed to compare clinical efficacy of polyhexanide/betaine gel with silver sulfadiazine in partial-thickness burn treatment. From September 2013 to May 2015, 46 adult patients with partial-thickness burn ≥10% total body surface area that were admitted to the Burn Unit of Siriraj Hospital within 48 hours after injury were randomly allocated into 2 groups. One group was treated with polyhexanide/betaine gel, and the other group was treated with silver sulfadiazine. Both groups received daily dressing changes and the same standard care given to patients with burns in this center. Healing times in the polyhexanide/betaine gel group and silver sulfadiazine group were 17.8 ± 2.2 days and 18.8 ± 2.1 days, respectively ( P value .13). There were no significant differences in healing times, infection rates, bacterial colonization rates, and treatment cost in both groups. The pain score of the polyhexanide/betaine gel group was significantly less than the silver sulfadiazine group at 4 to 9 days after treatment ( P < .001). The satisfactory assessment result of the polyhexanide/betaine gel group was better than that in the silver sulfadiazine group. These data indicate the need for adequately designed studies to elicit the full potential of polyhexanide gel as a wound dressing for partial-thickness burn wounds.

Clinical Efficacy Test of Polyester Containing Herbal Extract Dressings in Burn Wound Healing.

Technological advancement has assisted in developing various availabilities of wound products that help in not only in healing and preventing infection but also in providing patients' comfort and pain reduction during application. However, most of advanced wound healing products in Thailand were imported at high costs to patients. Nowadays, there are increased numbers of local researches of herbs that could provide healing environment for successful wound care. Herbal wound products are currently being introduced as alternatives to those imported dressings. The aim of this study was to report the clinical efficacy of using polyester containing herbal extract dressings in healing of second-degree burns. The volunteers were divided by simply randomized method into the study group of patient using polyester containing herbal extract dressing and the control group of patients treating with dressings that are commercially available and common use. The standard treatment protocols were performed at every 3 days of dressing change. Comparative evaluation consisted of time of healing, length of hospital stays, pain analog score assessment, percentage of infection, and descriptive notification of unfavorable clinical symptoms or signs or side effects.

Silk sericin ameliorates wound healing and its clinical efficacy in burn wounds.

The aim of this study was to evaluate the effect of silk sericin, a protein from silkworm cocoon, on scratch wound healing in vitro. For applicable result in clinical use, we also study the efficacy of sericin added to a standard antimicrobial cream, silver zinc sulfadiazine, for open wound care in the treatment of second-degree burn wounds. In vitro scratch assays show that sericin at concentration 100 µg/mL can promote the migration of fibroblast L929 cells similar to epidermal growth factor (positive control) at 100 µg/mL. After 1 day of treatment, the length of scratch in wounds treated with sericin was significantly shorter than the length of negative control wounds (culture medium without sericin). For clinical study, a total of 29 patients with 65 burn wounds which covered no less than 15 % of total body surface area were randomly assigned to either control (wounds treated with silver zinc sulfadiazine cream) or treatment (wounds treated with silver zinc sulfadiazine with added sericin cream) group in this randomized, double-blind, standard-controlled study. The results showed that the average time to reach 70 % re-epithelialization of the burned surface and complete healing in the treatment group was significantly shorter, approximately 5-7 days, than in the control group. Regarding time for complete healing, control wounds took approximately 29.28 ± 9.27 days, while wounds treated with silver zinc sulfadiazine with added sericin cream took approximately 22.42 ± 6.33 days, (p = 0.001). No infection or severe reaction was found in any wounds. This is the first clinical study to show that silk sericin is safe and beneficial for burn wound treatment when it is added to silver sulfadiazine cream.

Comparative clinical study of Bactigras and Telfa AMD for skin graft donor-site dressing.

The Bactigras(®) paraffin tulle coated with chlorhexidine is normally used for the treatment of donor-site wounds in burn patients who received split-thickness skin grafts in several centers. It has some disadvantages, such as adhesion to wound surfaces and pain from the irritation caused by this dressing. The Telfa AMD(®), a non-adherent wound dressing which consists of absorbent cotton fibers impregnated with polyhexamethylene biguanide enclosed in a sleeve of thermoplastic polymers, is a new option for donor-site wound care which causes less adherence to the wound. The purpose of this study was to compare clinical efficacy of these two dressings for the management of donor-site wounds. Thirty-two patients who received split-thickness skin grafts by donor site harvesting from the thigh were enrolled in this study and randomized into two groups receiving either the Bactigras(®) or the Telfa AMD(®) wound treatment. Re-epithelialization, pain, infection and cost-effectiveness analyses were compared between both groups. The results showed that there was no significant difference in age, area of donor sites or length of hospital stays between the groups (p > 0.05). However, the day of re-epithelialization (≥90%) was significantly shorter in patients treated with the Telfa AMD(®) compared to the Bactigras(®) group (14.00 ± 3.05 vs. 9.25 ± 1.88 days for Bactigras(®) and Telfa AMD(®) groups, respectively, p < 0.001). The average pain score was also significantly lower in the Telfa AMD(®) group (1.57 ± 0.55 vs. 4.70 ± 1.16, p < 0.001). There was no difference in the cost of treatment between the groups (4.64 ± 1.97 vs. 5.72 ± 2.54 USD, p = 0.19). This study indicated that the Telfa AMD(®) was an effective dressing for the treatment of donor-site wounds.

Efficiency of microbial cellulose dressing in partial-thickness burn wounds.

Microbial cellulose is a natural polymer that can hold a quantity of water without any disconformities. Therefore, it is proposed for use as wound dressing material. We report a case of 28% total body surface area partial-thickness flame burn: approximately 4.5% superficial partial-thickness burns on anterior face and 23.5% combined superficial and deep partial-thickness burns on both upper arms and anterior trunk. A microbial cellulose dressing, Nanocell (Thai Nano Cellulose Co Ltd, Bangkok, Thailand), was applied to the face wound only once, without any further dressing change. Progress of healing, until full epithelialization on the face, was observed for 2 weeks. During the treatment period, the patient did not show any irritation or allergic reaction to this new dressing, and wound swab culture showed no evidence of bacteria presence. This innovative material can be an alternative dressing for superficial partial-thickness burn wounds.

In vitro evaluation of the antimicrobial effectiveness and moisture binding properties of wound dressings.

A variety of silver-coated dressings and some impregnated with other chemicals are now available in the market; however, there have been few studies analyzing their comparative efficacies as antimicrobial agents. Moreover, their properties for retaining an appropriate level of moisture that is critical for effective wound healing have never been reported. Five commercially available silver-containing and chlorhexidine dressings, Urgotul SSD(®), Bactigras(®), Acticoat(®), Askina Calgitrol Ag(®) and Aquacel Ag(®), were tested to determine their comparative antimicrobial effectiveness in vitro against five common wound pathogens, namely methicillin-sensitive and -resistant Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. Mepitel(®), a flexible polyamide net coated with soft silicone, was used as a control. The zones of inhibition and both the rapidity and the extent of killing of these pathogens were evaluated. All five antimicrobial dressings investigated exerted some bactericidal activity, particularly against E. coli. The spectrum and rapidity of action ranged widely for the different dressings. Acticoat(®) had a broad spectrum of action against both Gram-positive and -negative bacteria. Other dressings demonstrated a narrower range of bactericidal activities. Regarding the absorption and release of moisture, Askina Calgitrol Ag(®) absorbed and released the most moisture from the environment. Aquacel Ag(®) also exhibited good moisture absorption and moisture release, but to a lower degree. The other tested dressings absorbed or released very little moisture. Askina Calgitrol Ag(®) and Aquacel Ag(®) are good alternative dressings for treating wounds with high exudates and pus. An understanding of the characteristics of these dressings will be useful for utilizing them for specific requirements under specified conditions.

Clinical effectiveness of alginate silver dressing in outpatient management of partial-thickness burns.

Askina Calgitrol Ag(®) (B. Braun Hospicare Ltd, Collooney Co. Sligo, Ireland), alginate silver wound dressing, is an advanced wound dressing which combines the potent broad-spectrum antimicrobial action of silver with enhanced exudate management properties of calcium alginate and polyurethane foam. The purpose of this study was to compare the efficacy of Askina Calgitrol Ag(®) and 1% silver sulfadiazine (1% AgSD) in the outpatient management of partial-thickness burn wounds at Burn Unit, Siriraj Hospital. A prospective descriptive study was conducted between January 2008 and January 2009 in Burn Unit, Division of Trauma Surgery, Siriraj Hospital, Mahidol University, Thailand. The 65 patients with partial-thickness burn wounds, less than 24 hours post-burn injury, had a total body surface area (TBSA%) less than 15% were treated at Siriraj Outpatient Burn Clinic. All patients were divided into Askina Calgitrol Ag(®) treated group (30 patients) and 1% AgSD treated group (35 patients). The data were compared by the demographics including age, gender, % TBSA burn, pain score, number of wound dressing change, nursing time and time of wound healing. Patients included in both groups were comparable with no significant differences in demographic data of age, gender, location of burn and type of burn injury (P > 0·05 evaluated by paired Student's t-test) between both group. The present results showed that average pain scores in the Askina Calgitrol Ag(®) treated group were significantly lower than the 1% AgSD treated group (2·23 ± 1·87 versus 6·08 ± 2·33, respectively) between both groups (P < 0·02). Patients treated with Askina Calgitrol Ag(®) had significantly lower number of wound dressing change (P < 0·02) and nursing time (P < 0·02) compared with 1% AgSD treated group. The Askina Calgitrol Ag(®) group needed less frequent wound dressing. Healing time was 7 ± 3·51 days after the application of Askina Calgitrol Ag(®). This was significantly shorter than that of control wounds (14 ± 4·18 days). Application of Askina Calgitrol Ag(®) leads to a good burn wound outcome. The present study confirms the effectiveness of Askina Calgitrol Ag(®) in the outpatient management of partial-thickness burn wounds.

A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns.

Silver sulfadiazine has been used as a topical burn wound treatment for many years. Pain associated with dressing changes is a common problem in burn wounds. Aquacel Ag, a hydrofiber dressing coated with ionic silver has been reported to reduce burn wound infection and promote antimicrobial activity. The purpose of this study was to show the benefits of Aquacel Ag for the treatment of partial thickness burns. This prospective randomized study was conducted in 70 patients who had partial thickness burns less than 15% of total body surface area and were treated at Siriraj outpatient burn clinic during December 2006-February 2008. Patients were divided into two groups: Aquacel Ag-treated group with dressing changes every 3 days (35 patients) and 1% silver sulfadiazine-treated group, with daily dressing changes (35 patients). There was no difference in demographic data including age, gender, burn percentage between groups. Time-to-wound healing pain score during dressing change and cost of treatment were compared between both groups. Time-to-wound closure was significantly shorter in the Aquacel Ag-treated group (10 +/- 3 versus 13.7 +/- 4 days, P < 0.02) as well as pain scores at days 1, 3 and 7 (4.1 +/- 2.1, 2.1 +/- 1.8, 0.9 +/- 1.4 versus 6.1 +/- 2.3, 5.2 +/- 2.1, 3.3 +/- 1.9, respectively, P < 0.02). Total cost of treatment was 52 +/- 29 US dollars for the Aquacel Ag-treated group versus 93 +/- 36 US dollars for the silver sulfadiazine-treated group. This study showed that Aquacel Ag increased time to healing, decreased pain symptoms and increased patient convenience because of limiting the frequency of replacement of the dressing at lower total cost. This study confirms the efficacy of Aquacel Ag for the treatment of partial thickness burns at an outpatient clinic.

Thoracic trauma at Siriraj Hospital 1997-2006.

Thoracic trauma is a common injury that has a high mortality rate. Fortunately, most can be treated by a simple maneuver as intercostal drainage (79.4%). During the decade 1997-2006, there were 897 admitted patients in the Trauma division of Siriraj Hospital. Most were men (85.5%) and the common age group was 21-30 years. Blunt trauma was the major type of injury (58.9%) and traffic accidents were common causes. Abdominal injury was the most common associated injury. After the management was improved, the overall mortality rate was reduced from 7.0% to 5.1%. Today, minimally invasive surgery such as laparoscopy can reduce hospital stays and pain in patients with thoracoabdominal injury.

Benefit of hydrocolloid SSD dressing in the outpatient management of partial thickness burns.

Silver sulfadiazine has been used as topical medication in the treatment of partial-thickness burns or secondary degree burns for many years. Pain during daily wound cleansing is the main problem. Urgotul SSD, a hydrocolloid dressing with silver sulfadiazine (SSD) has been reported to reduce infection and exhibit antimicrobial activity in burn wounds. The purpose of the present study was to compare the efficacy of Urgotul SSD and 1% silver sulfadiazine for treatment of partial thickness burn wounds. The authors reviewed 68 patients who had partial thickness burn wound less than 15% total body surface area (TBSA%) and were treated at Siriraj outpatient burn clinic during July 2005-December 2006. All patients were divided into two groups: Urgotul SSD treated group (34 patients) and 1% silver sulfadiazine treated group (34 patients). The two groups were compared by the demographic data including age, gender, % total body surface area (TBSA) burn, % TBSA deep burn, type of burn as well as percent of wound infection, total cost of wound dressing, pain medication, level of pain and time of wound healing. There were no differences in demographic data of age, % TBSA burn, % wound infection, total treatment cost of burn wound care (52 +/- 38 US$ for Urgotul SSD versus 45 +/- 34 US$ for silver sulfadiazine treated group). Time of wound closure was significantly shorter in the Urgotul SSD treated group (10 +/- 4 days in Urgotul SSD versus 12 +/- 6 in 1% silver sulfadiazine treated group) between both groups (p < 0.05). Average pain scores and pain medication in Urgotul SSD treated group was significantly lower than 1% silver sulfadiazine treated group (3 +/- 1 versus 6 +/- 2 and respectively, p < 0.05). All of the patients who developed wound infection responded well to targeted topical and oral antibiotic treatment. The authors conclude that Urgotul SSD has advantages of reducing pain symptom, pain medication requirement, increased patient convenience due to decreased time of follow-up at outpatient burn clinic, limiting the frequency of replacement of the dressing at comparable total cost and incidence of burn wound infection. The present study confirms the efficacy of Urgotul SSD in the treatment of partial thickness or secondary degree burn wound at the outpatient clinic.

Substance P enhances wound closure in nitric oxide synthase knockout mice.

INTRODUCTION: The neuropeptide, substance P (SP), up-regulates nitric oxide production (NO). The purpose of this study was to determine whether SP enhances response to cutaneous injury in nitric oxide synthase knockout (NOS null) mice. METHODS: We studied mice with targeted deletions of the 3 NOS genes, neuronal NOS, inducible NOS, or endothelial NOS. Full thickness dorsal wounds were treated daily (d 0-6) with topical SP or normal saline (NaCl). Wounds were analyzed by flow cytometry for macrophage, leukocyte, endothelial, and dendritic cells. Healing time and wound epithelialization were compared using analysis of variance. RESULTS: Wound closure in the 3 NOS null mice was slower than the control mice (P < 0.05). SP treatment enhanced wound closure in NOS null mice (P < 0.02). NOS null wounds exhibited reduced inflammation. SP increased macrophage, leukocyte, and dendritic cell densities at d 3 and d 7 (P < 0.05) in all NOS null mice. SP increased endothelial cell number in neuronal NOS and inducible NOS null mice, but not in endothelial NOS null mice (P > 0.05). CONCLUSIONS: SP ameliorated the impaired wound healing response observed in NOS null mice by enhancing wound closure kinetics and epithelialization. SP increased inflammatory cell density in the wounds supporting the essential role of inflammatory cells, especially macrophages, in wound repair.

Topical substance P increases inflammatory cell density in genetically diabetic murine wounds.

The neuropeptide substance P (SP) is a known inflammatory mediator released from cutaneous peripheral nerve terminals. SP effects on cellular composition in the cutaneous response to injury remain unclear. Based on our previous observations about SP effects on wound repair, we hypothesized that topical SP increases inflammatory cell density infiltration early after injury. A full-thickness 1.5 x 1.5 cm(2) wound was created on the dorsum of 8-9-week-old C57BL/6J-m+Lepr(db) mice (db/db). Wounds were treated daily with 300 muL of either normal saline (0.9% NaCl) or 10(-9) M SP for 7 days. Three wounds from each group were harvested at 2, 3, 7, 14, and 28 days. Samples underwent enzymatic digestion and were incubated with fluorescent-labeled antibodies. Using flow cytometry, cellular content and density for each sample was derived. Masson Trichrome stained histology specimens were prepared to confirm results. Cell density in the SP-treated wounds (11.3 x 10(7) cells/g tissue, standard deviation [SD]+/-1.5 x 10(7)) was greater than in NaCl-treated wounds (7 x 10(7) cells/g tissue, SD+/-2.3 x 10(7), p<0.05) at day 7 postwounding. SP significantly increased the density of leukocytes (2.1 x 10(7), SD +/-3.6 x 10(6) vs. 1.8 x 10(7), SD+/-4.9 x 10(5), p<0.02) 3 days after wounding and the density of macrophages (2.9 x 10(7), SD+/-7.5 x 10(6) vs. 1.3 x 10(7), SD+/-1.4 x 10(6), p<0.05) 7 days after wounding. There were no significant differences in endothelial cell, leukocyte, or macrophage density at later time points. Topical SP treatment increases early inflammatory density in the healing wounds of db/db mice. These data support a role for nerve-mediated inflammation in cutaneous wound repair.

Iatrogenic chylothorax in major burn patient: case report and literature review.

Chylothorax is a potentially life-threatening form of pleural effusion containing lymphatic fluid. Its etiology may be either traumatic (either post-operative or a direct result of injury), a congenital abnormality of the thoracic duct, or non-traumatic. This is a case report of a left iatrogenic chylothorax, which developed 2 days after internal jugular vein catheterization, in a patient with 50% total body surface area (TBSA) burns. This complication was treated successfully by tube thoracostomy and oral supplementation with a low fat, high carbohydrate, high protein diet. Further the authors review the etiology, pathogenesis, clinical presentation and recommended management of catheter-related chylothorax.

Making sense of hypertrophic scar: a role for nerves.

Healed partial thickness wounds including burns and donor sites cause hypertrophic scar formation and patient discomfort. For many patients with hypertrophic scars, pruritus is the most distressing symptom, which leads to wound excoriation and chronic wound formation. In spite of the clinical significance of abnormal innervation in scars, the nervous system has been largely ignored in the pathophysiology of hypertrophic scars. Evidence that neuropeptides contribute to inflammatory responses to injury include inflammatory cell chemotaxis, cytokine and growth factor production. The neuropeptide substance P, which is released from nerve endings after injury, induces inflammation and mediates angiogenesis, keratinocyte proliferation, and fibrogenesis. Substance P activity is tightly regulated by neutral endopeptidase (NEP), a membrane bound metallopeptidase that degrades substance P at the cell membrane. Altered substance P levels may contribute to impaired cutaneous healing responses associated with diabetes mellitus or hypertrophic scar formation. Topical application of exogenous substance P or an NEP inhibitor enhances wound closure kinetics in diabetic murine wounds suggesting that diabetic wounds have insufficient substance P levels to promote a neuroinflammatory response necessary for normal wound repair. Conversely, increased nerve numbers and neuropeptide levels with reduced NEP levels in human and porcine hypertrophic scar samples suggest that excessive neuropeptide activity induces exuberant inflammation in hypertrophic scars. Given these observations about the role of neuropeptides in cutaneous repair, neuronal modulation of repair processes at two extremes of abnormal wound healing, chronic non-healing ulcers in type II diabetes mellitus and hypertrophic scars in deep partial thickness wounds, may provide therapeutic targets.

Abdominal compartment syndrome monitoring in major burn patients with Siriraj device catheter.

Abdominal compartment syndrome (ACS) is consistently reported to have significant morbidity and mortality. Major burn patients who receive massive fluid resuscitation are at high-risk for this condition. Close monitoring of ACS is necessary for these patients. Prolonged unrelieved intra-abdominal pressure (IAP) at greater than 20 mmHg can produce significant morbidity and mortality. The most widely accepted and feasible way to measure IAP is via the draining port of a standard urinary catheter Siriraj burn unit developed its own device from simple equipment that can be found easily in the hospital. It proved to be useful, cheap, and effective in monitoring intra-abdominal pressure. The present study described techniques of using this device for monitoring and early detection of ACS. Five major burn patients > or = 40% Total body surface area (TBSA) was measured by IAP measurement via foley catheter using the Siriraj device catheter compared to direct measurement via peritoneal catheter. There was no difference of IAP between the two methods (p = 0.48). This suggested that Siriraj device catheter was useful, not invasive, and effective in reflection of actually IAP Siriraj burn unit suggested IAP measurement in all major burns > or = 40% TBSA to early recognize and treat intra-abdominal hypertension(IAH) that can lead to ACS. Early detection of this syndrome might decrease the adverse effects after increasing abdominal pressure that can cause organ dysfunction.