An in-vivo study of the wound-bursting strengths of octyl-cyanoacrylate, butyl-cyanoacrylate, and surgical tape in rats.

BACKGROUND: Several non-invasive wound-closure devices are available. Clinical studies of low-tension lacerations suggest similar clinical outcomes with these devices. OBJECTIVE: We compared the wound-bursting strengths (WBS) of octyl-cyanoacrylate (Dermabond), butyl-cyanoacrylate (Histoacryl Blue), and adhesive tape (Steri-Strips). METHODS: Design-randomized, controlled, blinded experiment. Setting-university-based division of laboratory animal research. Subjects-15 Sprague-Dawley rats weighing 250-350 g. Interventions-standardized 2-cm full-thickness incisions were made in duplicate on both sides of the rat's dorsum with a #15 surgical blade and closed with one of the three study wound-closure devices following manufacturer instructions. The order of closure was randomized. Measurements-WBS was measured after wound closure with a validated vacuum-controlled wound chamber device (BT-2000) that measures the pressure required to disrupt the closed wound. Data analysis-between-group comparisons were performed with pair-wise t-tests and chi-squared tests. This study had 80% power to detect a 75-mm Hg between-group difference in WBS (two-tailed alpha = 0.05). RESULTS: We evaluated 30 incisions in 15 rats. The mean WBS of octyl-cyanoacrylate (298 +/- 58 mm Hg) was significantly higher than that of butyl-cyanoacrylate (199 +/- 87 mm Hg; difference 98 mm Hg [95% confidence interval (CI) 32-165], p = 0.006) or Steri-Strips (129 +/- 67 mm Hg; difference 169 mm Hg [95% CI 112-227], p < 0.001). The WBS of butyl-cyanoacrylate was stronger than that of Steri-Strips; difference 71 mm Hg (95% CI 4-138), p = 0.035. CONCLUSIONS: Octyl-cyanoacrylate tissue adhesive has a higher WBS than butyl-cyanoacrylate, whose WBS is greater than that of surgical tape.

The effect of cyclodextrin-solubilized curcuminoids on amyloid plaques in Alzheimer transgenic mice: brain uptake and metabolism after intravenous and subcutaneous injection.

INTRODUCTION: Curcuminoids may improve pathological conditions associated with Alzheimer's disease. However, their therapeutic potential is limited by their exceedingly low bioavailability after oral administration. A method to deliver solubilized curcuminoids by injection was evaluated in Alzheimer transgenic mice. METHODS: Amyloid protein precursor (APP)SWE, PS1dE9 mice were intravenously or subcutaneously injected at weekly intervals between the ages of 4 and 12 months with serum- or cyclodextrin-solubilized curcuminoids to assess their potential for plaque prevention. Alternatively, mice between the ages of 11 and 12 months were intravenously injected with cyclodextrin-solubilized curcuminoids at biweekly intervals to evaluate their ability to eliminate existing plaques. Plasma and brain levels of curcuminoids and their metabolites were also determined after subcutaneous and intravenous injection. RESULTS: Weekly long-term injections did not result in a significant plaque load reduction. However, intravenous injection of cyclodextrin-solubilized curcuminoids at higher curcuminoid concentrations and at a biweekly frequency between the ages of 11 and 12 months reduced the plaque load to approximately 70% of the control value. After intravenous injection, plasma levels of 100 µM curcuminoids and brain levels of 47 nmol/g could initially be achieved that declined to essentially undetectable levels within 20 minutes. The primary curcuminoid metabolites in plasma were the conjugates of glucuronide or sulfate and hexahydrocurcuminoids as reduction products. In the brain, both hexahydrocurcuminoids and octahydrocurcuminoids were detected as major metabolites. After subcutaneous injection, maximal curcuminoid plasma levels of 23 µM and brain levels of 8 nmol/g were observed at 30 minutes after injection and curcuminoids remained detectable for 2 to 3 h. CONCLUSION: Curcuminoids are rapidly metabolized after injection and their effect on reducing plaque load associated with Alzheimer's disease may be dependent on the frequency of administration.

Controlled mild hypothermia prolongs survival in a rat model of large scald burns.

OBJECTIVES: Early surface cooling of burns reduces pain and depth of injury and improves healing. However, there are concerns that cooling of large burns may result in hypothermia and worsen outcomes. In contrast, controlled mild hypothermia improves outcomes after cardiac arrest and traumatic brain injury. The authors hypothesized that controlled mild hypothermia would prolong survival in a rat model of large scald burns. METHODS: Thirty-six Sprague-Dawley rats (250-300 g) were anesthetized with 40 mg/kg intramuscular ketamine and 5 mg/kg xylazine, with supplemental inhalational isoflurane as needed. A single full-thickness scald burn covering 40% of total body surface area was created on each of the rats using a Mason-Walker template placed in boiling water (100 °C) for a period of 10 seconds. The rats were then randomized to hypothermia (n = 18) or no hypothermia (n = 18). Core body temperature was continuously monitored with a rectal temperature probe. In the experimental group, mild hypothermia was induced by applying ice packs over the prone rats until their rectal temperature was reduced by 2 °C for a period of 2 hours. After 2 hours of hypothermia, the rats were rewarmed back to their baseline temperature with a heating pad. The control rats were not cooled. The rats were monitored until death or for a period of 7 days, whichever was greater. The primary outcome was time to death. The difference in survival between the groups was determined using Kaplan-Meier analysis and the log-rank test. RESULTS: Hypothermia was induced in all experimental rats within a mean of 22 minutes (95% confidence interval [CI] = 17 to 27). The numbers of nonhypothermic and hypothermic rats that were dead at each time point were as follows: 2 hours, five versus none; 18 hours, 16 versus five; 24 hours, 18 versus eight; and 48 hours, 18 versus 13 (p = 0.05). There were no additional deaths after 48 hours. The mean time to survival of the hypothermic rats was significantly greater than that of the nonhypothermic rats (p < 0.001). CONCLUSIONS: Induction of brief, mild hypothermia prolongs survival and increases the survival rate in nonresuscitated rats with large scald burns.

Rapid and selective enzymatic debridement of porcine comb burns with bromelain-derived Debrase: acute-phase preservation of noninjured tissue and zone of stasis.

Deep burns are associated with the formation of an eschar, which delays healing and increases the risk of infection. Surgical debridement of the eschar is, at present, the fastest means to achieve an eschar-free bed, but the process can not differentiate between the viable tissue and the eschar and follow the minute irregularities of the interface between the two. We evaluated the efficacy and selectivity of a novel enzymatic bromelain-based debriding agent, Debrase Gel Dressing (Debrase), in a porcine comb burn model. We hypothesized that Debrase would result in rapid debridement of the eschar without adverse effects on the surrounding uninjured skin. This is a prospective, controlled, animal experiment. Five domestic pigs (20-25 kg) were used in this study. Sixteen burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 x 20 mm full-thickness burns and separated by three 5 x 20 mm unburned interspaces representing the zone of stasis. The burned keratin layer (blisters) was removed, and the burns were treated with a single, topical, Debrase or control vehicle application for 4 hours. The Debrase/control was then wiped off using a metal forceps handle, and the burns were treated with a topical silver sulfadiazine (SSD). The wounds were observed, and full-thickness biopsies were obtained at 4 and 48 hours for evidence of dermal thickness, vascular thrombosis, and burn depth, both within the comb burns and the unburned interspaces in between them. Chi-square and t tests are used for data analysis. A single 4-hour topical application of Debrase resulted in rapid and complete eschar dissolution of all the burns in which the keratin layer was removed. The remaining dermis was thinner (1.1 +/- 0.7 mm) than in the control burns (2.1 +/- 0.3 mm; difference 0.9 mm [95% confidence interval: 0.3-1.4]) and was viable with no injury to the normal surrounding skin or to the unburned interspaces between the burns, which represents the zone of stasis. In control burns, the entire thickness of the dermis was necrotic. At 48 hours, Debrase-treated areas were found partially desiccated under SSD treatment. The unburned interspaces demonstrated partial-thickness necrosis in two third and full-thickness necrosis in one third of wounds. In contrast, full-thickness necrosis was noted in all control interspaces (P = .05). In a porcine comb burn model, a single, 4-hour topical application of Debrase resulted in rapid removal of the necrotic layer of the dermis with preservation of unburned tissues. At 48 hours, SSD treatment resulted in superficial tissue damage and partial preservation of the unburned interspaces.

Healing of mid-dermal burns in a diabetic porcine model.

Wound healing is delayed in diabetic patients. We developed a diabetic-porcine burn model and compared the healing of partial-thickness burns in normal and diabetic pigs. We hypothesized that wound healing would be delayed in the diabetic swine. Diabetes mellitus was chemically induced in three domestic pigs (25-50 kg) by intravenous injection of streptozotocin 130 mg/kg over 30 minutes. Glucose levels were maintained between 250 and 500 mg/dl by injecting short-acting or long-acting insulin 1 unit/kg daily as needed. Three weeks later, 14 partial-thickness burns were created on the backs and flanks of each of the anesthetized pigs with a 2.5 x 2.5-cm aluminum bar preheated to 80 degrees C and applied for 20 seconds. A similar number of burns were created on three control nondiabetic pigs. The burns were treated with a topical antibiotic, and 3-mm full-thickness biopsies were taken from all wounds at 7, 10, 14, and 21 days for histomorphologic evaluation using hematoxylin and eosin staining by a board-certified dermatopathologist masked to the type of pig. The main outcome was the percentage of the wound in cross section that was reepithelialized. Comparison of outcomes between normal and diabetic pigs was performed with Student's t-tests. The diabetic pigs gained less weight, and their skin was considerably thinner than in the control pigs. Although the absolute depth of the burns was similar, the relative depth was greater in the diabetic pigs. The percentage of wound reepithelialization was lower in diabetic than in normal pigs at 7 days (1.8% [95% CI: 0-5.5] vs 65.0% [95% CI: 54.2-75.9]; P < .001) as well as at 10 days (19.2% [95% CI: 6.0-32.4] vs 76.9% [95% CI: 59.8-94.0]; P < .001) and 14 days (43.9% [95% CI: 30.4-57.4] vs 99.9% [95% CI: 92.6-100]; P < .001). All burns were completely reepithelialized at 21 days, and none of the wounds were infected. Reepithelialization of partial-thickness burns is delayed in streptozotocin-induced diabetic pigs when compared with normal pigs. It is unclear whether the delay in healing is due to the thinner skin or the metabolic consequences of diabetes or their combination.