Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin.

Inhibition of wound contraction by topical anti microbial agents has been described. The purpose of this study was to further investigate that phenomenon and to explore the effect that other agents such as Aloe vera might have on this process. Full-thickness excised wounds were created on the dorsum of Sprague-Dawley rats under anaesthesia. The wounds were treated with topical agents three times daily for fourteen days, then observed until healed. Groups were: saline control, placebo (aqueous cream) control, silver sulphadiazine (SSD) cream 1%, SSD 0.5%, SSD 1% with Aloe vera, SSD 1% with nystatin, nystatin. Wound surface areas were measured each three days. Time to 50% and 90% healing was compared using ANOVA. Wound half-life and healing times were shortest in the SSD/Aloe vera and nystatin groups (P<0.05) and longest in the 1% SSD and saline control groups. The placebo group (aqueous cream) healed in a significantly shorter time (P<0.05) than the control (saline) group. Wound contraction was delayed by saline and SSD. Nystatin and Aloe vera, when added to SSD, reversed that effect. These data suggest that a dry wound (saline) heals slowly. Infection control without delay of wound healing is most appealing and clinical trials are planned.

Cadaveric allograft discards as a result of positive skin cultures.

INTRODUCTION: The availability of cadaveric allograft is often limited by potentially pathogenic microbial organisms. Little data exists on cadaveric allograft discard rates related to positive microbiology. The purpose of this retrospective review was to determine the cadaveric allograft discard rates related positive microbiology and the subsequent breakdown of those organisms involved. METHODS: From January 1995 to June 1997, 1112 donors were screened and procured after informed consent had been obtained. The procedures used were in accordance with American Association of Tissue Banks (AATB) standards and guidelines. The number of discards due to positive skin cultures was reviewed and analyzed for type of microbial organism. RESULTS: Fifty-four donors (4.9%) were discarded due to positive skin cultures. Methicillin resistant Staphylococcus epidermidis, (MRSE), was the most predominant organism (22.2%), followed by gram negative rods as a group (18.5%), with Aspergillus species being the least predominant isolate. CONCLUSION: Despite the strict adherence to AATB protocol, microbial contamination of cadaveric allograft skin does not reach zero. It is not surprising that S. epidermidis was the predominant isolate, since skin is one of its common habitats. Continued vigilance in microbial testing remains paramount to ensure the quality of the allograft.

Cadaver donor discards secondary to serology.

The use of cadaveric skin has made a major impact in the survival of patients experiencing major thermal injury. However, the availability of cadaveric skin is often limited by potentially pathogenic organisms. Very little data exists as to why cadaveric skin from donors who have been previously screened was discarded. From March 1994 to March 1996, 813 donors were referred to our tissue bank. All donors were reviewed for the cause of death, history and physical, and social history. One hundred fifty-three donors screened were discarded. Sixty-one donors of this group were discarded because of positive serologies. The following are the percentages of the specific positive serologies: hepatitis B core antibody, 52.3%; hepatitis B surface antigen, 18.1%; hepatitis C virus antibody, 14.3%; human immunodeficiency virus antibody, 4.9%; human T lymphocyte virus antibody, 4.9% and syphilis, 5.5%. Retrospectively, all donor screening questionnaires were reviewed for possible indicators in relation to positive serologic testing. Current screening methods, although excellent in social screening, still fail to identify a significant number of donors who may have positive serologies because of hepatitis, human immunodeficiency virus, human T lymphocyte virus, or syphilis. As the field of tissue banking continues to evolve, the focus will need to be directed toward better screening mechanisms in order to decrease our current discard rates after donors have been approved through the screening process.

The effects of hyperglycemia on skin graft survival in the burn patient.

The authors elected to determine the relative effects of hyperglycemia and/or elevated wound Gram-positive bacterial counts on success of skin graft survival in 74 burn patients. Results of serum glucose and quantitative wound biopsies on the day of admission and on postoperative day 4 were charted. Cases were separated into the following groups for analysis: normoglycemia plus normal bacterial counts, elevated bacterial counts only, hyperglycemia only, and hyperglycemia plus elevated bacterial counts. Successful graft "take" was defined as survival of 80% to 100% of the grafted area as assessed on postoperative day 4. Significant results included decreased incidence of graft take for groups with hyperglycemia only (62.5%), elevated bacterial counts only (63.3%), as well as hyperglycemia plus elevated bacterial counts (54.5%) when compared with the group with normoglycemia plus normal bacterial counts (92.8%; p = 0.020, p = 0.042, p = 0.012 respectively) for physiological parameters measured on postoperative day 4 only. Additionally, incidence of graft take was reassessed and found to be decreased significantly in groups with hyperglycemia (60.0%) vs. groups with normoglycemia (84.6%), regardless of Gram-positive bacterial counts (p = 0.034).

Biobrane improves wound healing in burned children without increased risk of infection.

A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.

Angiotensin II inhibitor DuP753 attenuates burn- and endotoxin-induced gut ischemia, lipid peroxidation, mucosal permeability, and bacterial translocation.

OBJECTIVE: To investigate the role of angiotensin II as a mediator of burn- and sepsis-induced gut ischemia and reperfusion injury and to determine whether treatment with the angiotensin II inhibitor DuP753 can attenuate mucosal injury and bacterial translocation in a burn/endotoxemia porcine model. SUMMARY BACKGROUND DATA: Thermal injuries and endotoxemia have been shown to induce ischemia and reperfusion injury to the intestine, leading to increased mucosal permeability and bacterial translocation. Angiotensin II, the production of which has been reported to increase after burn, is thought to be one of the primary mediators of postburn mesenteric vasoconstriction. METHODS: An ultrasonic flow probe was inserted into the superior mesenteric artery and a catheter into the superior mesenteric vein in 21 female pigs. After 5 days, all animals were anesthetized, and 14 received 40% total body surface area third-degree burn. DuP753 was administered intravenously at 1 microg/kg to seven pigs immediately after burn. Eighteen hours after burn, 100 microg/kg Escherichia coli lipopolysaccharide (LPS) was intravenously administered. Systemic and splanchnic hemodynamics were measured and blood samples were drawn for blood gas analysis. Plasma conjugated dienes (PCDs), an index of lipid peroxidation, were measured every 6 hours. Intestinal permeability was assessed every 6 hours by measuring the lactulose/mannitol excretion ratio. At the end of the study (42 hours), tissue samples were harvested for bacteriologic cultures. RESULTS: Burn caused a significant decrease in mesenteric blood flow, to approximately 58% of baseline. Postburn endotoxemia significantly reduced the blood flow in the superior mesenteric artery to 53% of baseline. Treatment with DuP753 prevented postburn vasoconstriction and subsequently abrogated the impact of postburn endotoxemia on blood flow in the superior mesenteric artery. Mesenteric oxygen supply was significantly reduced after burn and endotoxin to 60% and 51% of baseline levels, respectively. DuP753 administration significantly improved mesenteric oxygen supply after both insults. Burn- and LPS-induced mesenteric hypoxia, as indicated by decreased mesenteric oxygen consumption, was also ameliorated by DuP753 treatment. PCD levels were significantly elevated 8 hours after burn. LPS caused a higher and prolonged increase in PCD levels. Treatment with DuP753 significantly reduced PCD levels after burn and after LPS. Intestinal permeability, as assessed by the lactulose/mannitol ratio, showed 6-fold and 12-fold increases after thermal injury and LPS, respectively. In contrast, the lactulose/mannitol ratio was only doubled in DuP753-treated animals. Bacterial translocation was significantly increased after burn and endotoxin. The incidence of bacterial translocation in the DuP753-treated animals was similar to that in the sham group. CONCLUSIONS: Angiotensin II appears to play a pivotal role in the burn- and endotoxin-induced intestinal ischemia and reperfusion injury, with subsequent increases in permeability and bacterial translocation. Postburn administration of the angiotensin II receptor antagonist DuP753 significantly reduces the extent of these events.

Infestations and chronic infections in foreign pediatric patients with burns: is there a role for specific protocols?

Infestations by parasites such as Mycobacterium tuberculosis and other viral infections are common in third world countries. Consequently, the admission of a significant number of foreign patients to burn centers in the United States may pose new problems, not only for inpatients but also for health care workers. To document infestations in patients from third world countries and to determine the need for specific protocols, we studied 62 consecutive foreign patients admitted to our pediatric burn reconstruction service between July 1997 and December 1998. All patients were evaluated with chest X-ray, hemogram with differential count, clinical and laboratory nutritional assessment, and skin test for tuberculosis, and stool samples were evaluated for ova and parasites. No pathologic findings were seen on chest radiographs. Only 1 patient had a positive skin test for tuberculosis, as a result of previous bacille Calmette-Guérin vaccine. Yet, 10 patients (16%) had positive stool cultures for ova and parasites that contained 29 isolates. The most frequently identified organism was Blastocystis hominis. All amoebas identified were nonpathogenic according to Centers for Disease Control criteria. Ascaris lumbricoides and 1 case of cysticercosis were found. None of the patients with parasites had clinical manifestations of parasitosis or chronic infections. However, parasite infestations had a positive correlation with eosinophilia, altered nutritional status, and altered mean corpuscular hemoglobin concentration, as defined by multiple linear regression. Although foreign patients admitted to burn centers from third world countries have a low rate of infestations, patients at risk can be identified by laboratory findings and studies of nutritional status. Simple hand washing prevents the spread of disease and protects health providers.

The effect of denervation on leukocyte function in soft tissue infection.

BACKGROUND: The present study was undertaken to investigate the effect of denervation on leukocyte function in soft-tissue infection in an isolated in vivo ovine flap model. METHODS: Fifteen adult ewes were divided into three groups. An island pedicle flap was raised on the right buttock. In group I (no denervation), the cutaneous nerve remained intact, whereas in group II (acute denervation) the nerve was divided acutely. In group III (prolonged denervation) the nerve was divided 7 days before flap elevation. All flaps received intradermal inoculation of 10(7) Staphylococcus aureus, and the animals were observed for 96 hours. RESULTS: In both groups II and III, the leukocyte chemiluminescence and chemotaxis were significantly decreased when compared with group I. Furthermore, there was profound impairment of leukocyte functions in group III compared with group II. Group III also had significantly higher bacterial counts, larger septic foci, lower viable leukocyte ratios, and decreased bacterial killing compared with group I. CONCLUSIONS: Denervation, particularly over a period of time, results in increased bacterial growth of soft-tissue septic foci. This appears to be due to decreased leukocyte function resulting in diminished bacterial killing.

Modified Dakin's solution for cutaneous vibrio infections.

Vibrio species, specifically Vibrio vulnificus, are known to be endemic to warm saltwater environments. As a human pathogen they are capable of causing severe, progressive, necrotizing infections. The lesions are bullous in nature and often require wide surgical debridement due to the aggressiveness of this organism. The literature supports prophylactic antibiotic therapy for those with preexisting hepatic dysfunction or immunocompromise. The authors routinely implement prophylactic antibiotic coverage with doxycycline 100 mg every 12 hours for vibrio in patients with wounds exposed to or acquired in saltwater. In addition, they institute topical therapy with 0.025% sodium hypochlorite solution (modified Dakin's), based on their in vitro study of vibrio sensitivity to antimicrobials. Over the past 2 years, the authors have treated 10 patients with this protocol for cutaneous vibrio infections confirmed by quantitative cultures. None of these patients experienced progression of infection requiring operative debridement-contrary to the aggressive nature of this organism documented in other reports.

Topical nystatin powder in severe burns: a new treatment for angioinvasive fungal infections refractory to other topical and systemic agents.

Angioinvasive fungal infections have a significant morbidity and mortality in the immunocompromised host. Massive burns produce a profound derangement in cellular immunity along with a loss of cutaneous barrier function. Treatment of fungal burn wound infections poses a difficult therapeutic challenge. We present a new method of treatment for angioinvasive fungal infections with nystatin powder at a concentration of 6,000,000 units/g. It proved to be efficacious in four consecutive severely burned patients affected by massive angioinvasive fungal infection. Both superficial and deep tissue infections were eradicated without any other therapeutic interventions or adverse effects on wound healing.

The use of a modified Dakin's solution (sodium hypochlorite) in the treatment of Vibrio vulnificus infection.

We report the first clinical use of a modified Dakin's solution (0.025% sodium hypochlorite [NaOCl]) to halt the progress of severe cutaneous Vibrio vulnificus infection in a critically ill patient. The regimen used arose from an initial in vitro study designed to examine the sensitivity of Vibrio species to topical antimicrobial agents. Twenty-eight wound isolates were tested against the following eight topical preparations: silver sulfadiazine (Silvadene), nitrofurazone, mupirocin ointment (Bactroban), polymyxin B/bacitracin, mafenide acetate (Sulfamylon), nystatin/Silvadene, nystatin/polymyxin B/bacitracin, and 0.025% NaOCl solution. The results showed that V vulnificus, along with the other 18 Vibrio species tested, was most sensitive to the modified NaOCl solution.

Comparison of wound culture and bronchial lavage in the severely burned child: implications for antimicrobial therapy.

BACKGROUND: The relationship of the burn wound flora to microbial pathogens in the tracheobronchial tree has important implications for antimicrobial therapy in the severely burned patient. Management of septic complications is bolstered by surveillance quantitative wound cultures (QWC) and bronchial lavage fluid (BLF) cultures. OBJECTIVES: To compare the organisms present in BLF with those found in QWC and to determine if QWC can predict BLF results. DESIGN: Results of BLF cultures from all patients who underwent bronchial lavage from January 1, 1996, to December 31, 1996, at our institution were compared with QWC data from the same date. Criteria for a positive match included an identical antibiotic susceptibility pattern and biotype. Match rates were calculated qualitatively and quantitatively. RESULTS: In 30 (48%) of the 62 BLF cultures, there was a match between the organism identified in the BLF and the QWC. When strict quantitative criteria were applied, the match rate was only 9 (14%) of 62. Burn size and inhalation injury had no significant effect on match rate. CONCLUSIONS: Whereas the microbial pathogens were similar in the QWC and BLF, linear regression showed no value of QWC in predicting BLF culture results. The difference between qualitative and quantitative match rates suggests cross-colonization between the burn wound and tracheobronchial tree, but little to no cross-infection. The QWC and BLF cultures must be performed independently in determining antimicrobial specificity in the burned patient.

Is the limulus amebocyte lysate the sole predictor of septic episodes in major thermal injuries?

Septic episodes in thermal injuries are usually hallmarked by a series of physiologic parameters that include tachypnea, prolonged paralytic ileus, hyperthermia or hypothermia, altered mental status, thrombocytopenia, leukocytosis or unexplained leukopenia, acidosis, and hyperglycemia. Recent studies with polycystic kidney disease have clearly indicated that the limulus amebocyte lysate (LAL) assays were predictive of fungal infections in this patient population. Because both bacteria and fungi produce lipopolysaccharide that can be identified with the LAL assay, we randomly assayed sequential sera of 45 patients with major thermal injuries for positivity in the LAL assay, with use of the QCL-1000 kit (BioWhittaker, Walkersville, Md). The average burn size of this patient population was 63.43% total body surface area. The average age of the patient was 6.2 years. The sex distribution included 30 males and 15 females. The infectious agents included gram-positive cocci and gram-negative rods, and 14 patients had concomitant fungal infections. Eighty-five percent of the patients tested were positive for endotoxin, with levels ranging from < 0.1 EU/mL to > 1.0 EU/mL. The predominant organism isolated before or on the date the serum was drawn was Pseudomonas aeruginosa (51%), followed by Klebsiella pneumoniae (15%). The remaining 34% were a variety of Enterobacteriaceae. Of the 14 patients who yielded a fungus, 3 had negative LAL assays. Two patients with an elevated LAL grew only Staphylococcus epidermidis in the bloodstream and the wounds. These data clearly indicate that the LAL assay cannot be relied on as the sole predictor of septic episodes; however, it can be an adjunctive test to confirm sepsis when the other parameters have been considered.

Ciprofloxacin as a therapeutic modality in pediatric burn wound infections: efficacious or contraindicated?

BACKGROUND: Food and Drug Administration regulations state that ciprofloxacin hydrochloride may cause arthropathies. For this reason, such therapy is contraindicated in the pediatric population. However, several studies in children with cystic fibrosis have found the drug to be efficacious. Our hypothesis was that ciprofloxacin treatment is justified in the case of multiresistant organisms in burn populations. DESIGN: During a 4-year period (January 1, 1993, to December 31, 1997) we treated 56 of our pediatric burn patients with ciprofloxacin when cultures proved resistant to other antibiotics. The burn area was 65% of the total body surface area. The average patient age was 8.4 years. Of the 56 patients who received ciprofloxacin, 50 received the recommended dose. Biopsy specimens were assessed for quantitative bacteriology and antibiotic sensitivity. Radiologic review was conducted to examine for arthropathy. RESULTS: All patients showed unequivocal reduction in quantitative bacterial counts, and susceptibility to ciprofloxacin remained stable without the development of resistance. Of the 56 patients treated, 42 had a major reduction in their quantitative wound biopsies from 10(6) to less than 100 colonies per gram of tissue, while the remaining 14 were observed to have a 2- to 3-log decrease. No arthropathy was detected in any of the 56 patients receiving ciprofloxacin. Review of the patients' charts showed no documented adverse events associated with the use of ciprofloxacin. All patients survived their thermal injury and the complications associated with it without any untoward problems or complications of arthropathy. CONCLUSION: On the basis of these data, ciprofloxacin therapy in the treatment of immunosuppressed pediatric burn patients is efficacious and does not cause arthropathy.

Protection against exotoxin A (ETA) and Pseudomonas aeruginosa infection in mice with ETA-specific antipeptide antibodies.

Pseudomonas aeruginosa is an opportunistic pathogen that causes serious and sometimes fatal infections in the compromised host, especially in patients with major trauma or thermal injuries. Exotoxin A (ETA) is the major and most lethal virulence factor produced by this ubiquitous microorganism. In a recent study (H. S. Elzaim, A. K. Chopra, J. W. Peterson, R. Goodheart, and J. P. Heggers, Infect. Immun. 66:2170-2179, 1998), we identified two major epitopes, one within the translocation domain (amino acid [aa] residues 289 to 333) of ETA and another within the enzymatic domain (aa 610 to 638), by using a panel of antipeptide antibodies. Synthetic peptides representing these two epitopes induced ETA-specific antibodies which were able to abrogate the cytotoxic activity of ETA, as measured by incorporation of [3H]leucine into 3T3 fibroblasts. In the present study, these antibodies were tested for the ability to provide protection against ETA and infection with a toxin-producing strain of P. aeruginosa in a mouse model. Antibodies to either of the synthetic peptides conferred protection against ETA. Also, when used for immunization, both peptides induced active immunity to ETA in mice. Antibodies to the peptide representing a region within the enzymatic domain of ETA, in combination with the antibiotic amikacin, enhanced the survival of mice infected with a toxin-producing strain of P. aeruginosa. Thus, antipeptide antibodies specific for ETA might be paired with antibiotic treatment for passive immunization of patients suffering from P. aeruginosa infection.

Alternate antimicrobial therapy for vancomycin-resistant enterococci burn wound infections.

Survival after a major thermal burn is precarious and fraught with difficult complications associated with hypermetabolism, gut or respiratory dysfunction, and infection. Clinicians must be cognizant of a new threat to the patient with burn injuries--the emergence of vancomycin-resistant enterococci (VRE). In an analysis of 31 clinical isolates obtained during acute burn hospitalization, an optimal antimicrobial therapy for VRE has been identified. All VRE cultures were inoculated to the MicroScan Gram-Positive Breakpoint Combo Panel #8 (Dade Microscan, Inc, Sacramento, Calif), which speciates the enterococci, provides antimicrobial susceptibility patterns (including vancomycin) and a biotype, and examines streptomycin and gentamicin synergy. Eleven (35.5%) of the 31 isolates were identified as E faecium and 20 (64.5%) as E faecalis. All isolates were susceptible to chloramphenicol and tetracycline, whereas only half were sensitive to gentamicin synergy screen. All other antimicrobials screened against VRE were either ineffective or of limited effect. Our preliminary data supports the initiation of chloramphenicol therapy when a VRE burn wound infection is encountered or suspected.

Generation of neutralizing antipeptide antibodies to the enzymatic domain of Pseudomonas aeruginosa exotoxin A.

Burn patients suffer a break in the physical barrier (skin), which, when combined with their generalized state of immunodeficiency, creates an open window for opportunistic infections, mainly with Pseudomonas aeruginosa. Infection of the burn wound has always been a major factor in retardation of wound healing, and sepsis remains the leading cause of death in burn patients. Because studies have shown that topical treatment with antiexotoxin A (ETA) antibodies significantly increases survival in rats infected with toxin-producing strains of P. aeruginosa, we examined 11 synthetic peptides encompassing 12 to 45 amino acid (aa) residues, representing what were predicted by computer analysis to be the most hydrophilic and antigenic regions of ETA. These synthetic peptides were injected into rabbits for antibody production. Different groups of rabbits were immunized with a combination of peptides, with each combination representing one of the three distinct domains of ETA. Animals immunized with various peptide combinations produced peptide-specific antibodies that exhibited cross-reactivity to ETA. Two major epitopes were identified on the ETA molecule by experiments with peptide-specific antibodies in enzyme-linked immunosorbent assay and immunoprecipitation. One of these epitopes was located in the translocation domain (II) (aa 297 to 310), while the other was mapped to the last 13 aa residues at the carboxy-terminal end of the enzymatic domain (III) (aa 626 to 638). Of these two regions, the epitope in the enzymatic domain induced a much higher level of neutralizing antibodies that abrogated the cytotoxic activity of ETA in vitro. Antibodies to this epitope blocked the ADP-ribosyltransferase activity of ETA and appeared to interfere with binding of the substrate elongation factor 2 to the enzymatic active site of the ETA molecule. We conclude that polyclonal, as well as monoclonal, antibodies to short peptides, representing small regions of ETA, may have therapeutic potential in passive immunization or topical treatment of burn patients infected with toxin-producing strains of P. aeruginosa.

Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model.

PURPOSE: Many systemic and topical therapeutic agents such as growth hormone, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin-like growth factor (IGF) have been used as vulnerary agents. However, the role of nitric oxide (NO) as a wound-healing stimulant has been received with mixed reviews. NO is a potent vasodilator that is thought to be an endothelium-dependent relaxing factor, and a regulator of blood pressure and regional blood flow. It affects vascular smooth muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Therefore we compared the effects of several topical substances that have similar or reverse properties. METHODS: Using the excisional rat wound model, we evaluated the topical effects of Dermaide Aloe (D-Aloe, Dermaide Research Corp, Palos Heights, IL), nitroglycerin, Aquaphor (Beuersdorf, Inc., Norwalk, CT) alone, with D-Aloe with nitroglycerin, 2%, and L-NAME (NO inhibitor) with Aquaphor, and L-NAME with Aquaphor and D-Aloe for a 21-day period. All wounds were measured by planimetry at 1, 7, 10, 13, 16, 18, and 21 days. RESULTS: At day 1, all wounds had an average wound size of 2.27 cm2 (SD +/- 0.372) with no significant difference in wound size among the groups. Topically applied D-Aloe appeared to promote wound healing faster than the remaining other topicals (p < .05, Student-Newman-Keuls and Dunn's Method) over the study period. However, topicals combined with D-Aloe, the vehicle Aquaphor, and L-NAME improved the wound healing process when compared with nitroglycerin alone (p < .05). CONCLUSIONS: D-Aloe appears to have a wound-healing advancement factor that can reverse the effects of petrolatum- and nitroglycerin-based products as observed in the remaining groups when compared with nitroglycerin alone. It appears that D-Aloe's effect of preventing dermal ischemia by reversing the effects of thromboxane synthetase (TxA2) may act synergistically with NO or could be an oxygen radical scavenger.