Effects of immunosuppressive therapy on the induction of skin tumors by ultraviolet irradiation in hairless mice

The effects of therapy with four commonly used immunosuppressants--azathioprine, prednisolone, cyclophosphamide, and cyclosporine, on (UVI)-induced skin carcinogenesis were studied in the albino hairless (HRA/Skh-1) mouse. Following 30 weeks' exposure to UVI (290-400 nm) alone, 87% of mice developed skin tumors; the mean incidence of tumors at that time was 2.4 per mouse; and the tumors were predominantly papillomas (72%), with the remainder being carcinomas (25%) and keratoacanthomas (3%). Mice received immunosuppressive drug therapy beginning shortly after the start of UVI and continuing for up to 28 weeks. All drugs were given at immunosuppressive levels and dosages were comparable on a body weight basis to those used in clinical transplantation. Prednisolone had no effect on UVI-induced tumor development. Cyclosporine caused a moderate reduction in the latent period for tumor induction. Azathioprine and cyclophosphamide had strong promoting effects; the latent period for tumor induction was shortened and the tumor yield per mouse was increased (4.3 and 5.7 tumors per mouse, respectively, at 30 weeks after the start of UVI). Azathioprine, but not cyclophosphamide, also induced a larger proportion of carcinomas (43% and 15%, respectively). The results suggest that for kidney transplant recipients treated with the standard immunosuppressive drug regimen of azathioprine/prednisone, the increased susceptibility of the sun-exposed skin of these patients to squamous cell carcinoma is likely to be contributed to by specific promotion by the azathioprine therapy of the carcinogenic effects of sunlight.     

Evidence that 1 per cent Meshushit ointment prevents progressive dermal ischaemia of experimental deep partial skin thickness burns: a preliminary, quantitative controlled study

This study quantitatively assessed the topical effects of Meshushit, a new herbal compound, on the healing process of experimental deep partial skin thickness burns over 27 days. To symmetrical circular burns were inflicted on the back of 15 animals by aluminium templates. The Meshushit and its control vehicle containing 0.1 per cent gentamycin or the control vehicle plus antibiotic alone, were applied topically to randomly selected burns at equal time intervals. Epithelialization and contraction were assessed on postburn days 6, 10, 15, 18, 22 and 27 using a computerized planimeter. The newly formed granulation tissue was assessed histologically on postburn day 27, while the hair follicles were counted in the same sections. Student's t test was used to differentiate the rates of contraction and epithelialization; hair follicle counts and the thickness of the newly formed granulation tissue. None of the animals died during the experiment. The epithelialization and contraction rates did not differ significantly between the test groups. The Meshushit-treated wounds showed a significantly thicker granulation tissue layer as compared to its control (828.72 +/- 46.39 microns vs. 540.78 +/- 37.81 microns, P less than 0.01). The count of hair follicles was significantly higher in the Meshushit-treated burns (23.38 +/- 1.84 vs. 3.76 +/- 0.35, P less than 0.001). It is concluded that the herbal Meshushit ointment enhanced the newly formed granulation tissue and preserved better the hair follicles in the present burn wound model. It is suggested that these findings are due to the preservation of the dermal microcirculation.     

Mechanisms of joint damage in gout: evidence from cellular and imaging studies

The clinical course of gout is initially characterized by acute self-limited joint inflammation, but long-standing disease is often associated with chronic inflammation followed by the development of erosive joint damage, which can result in long-term functional impairment. Preventing joint damage is now a major focus of therapeutic intervention in gout. New light has been shed on the mechanisms leading to cartilage and bone damage in patients with this disease. Here, we discuss basic science studies focusing on the cellular immunology of bone and cartilage in gout and the effects of monosodium urate crystals on signaling pathways, cytokine release and the function of osteoclasts, osteoblasts and chondrocytes. We then explore the use of advanced imaging modalities (including MRI, ultrasonography, CT and dual-energy CT) to investigate pathology in gout, as they provide new ways to visualize joint tissues. These modalities vary in their ability to detect the various pathological features of gout and have different clinical applications. Imaging provides information about the inflammatory nature of the joint lesion, position and size of tophaceous deposits, and extent of bone and cartilage damage. Imaging is also increasingly being used to monitor the progression of joint damage and regression of tophi with effective urate-lowering therapy.     

Analytical method to examine the effects of carbon dioxide lasers on skin: a study using wrinkles induced in hairless mice

BACKGROUND AND OBJECTIVE: Investigation of the wrinkle smoothing process elicited by CO(2) laser treatment is important for understanding the mechanism involved in their repair. STUDY DESIGN/MATERIALS AND METHODS: Hairless mice with wrinkles induced in their dorsal skin by long-term exposure to ultraviolet radiation in the wavelength range of 290-320 nm were treated with a CO(2) laser. By using this model, we investigated the external appearance, histologic changes, and the mechanical properties of the skin during the wrinkle repair. RESULTS: Laser treatment with an appropriate intensity caused wrinkles to smooth completely. In the healing process, reepithelialization and collagen tissue regeneration in the upper dermis was observed. However, marked changes in the skin were noted, such as increases in the collagen layer and in the skin thickness, and changes in the mechanical properties of the skin, despite the favorable external appearance. CONCLUSIONS: An abnormal state characterized by excessive collagen regeneration and other changes in the dermis occur concomitantly with wrinkle smoothing.     

Nickel-induced oxidative stress in testis of mice: evidence of DNA damage and genotoxic effects

Oxidative stress (OS) mechanisms are speculated to play a significant role in nickel-induced toxic effects and their carcinogenic potency. Although nickel-induced oxidative damage in somatic tissues is well demonstrated, evidence of the involvement of a similar mechanism(s) in nickel-induced testicular dysfunction and associated genotoxic effects is scarce. Hence, the present study aimed to investigate the nickel-induced OS response in testis and the associated genotoxic implications in vivo. Initially, the toxicity profile of nickel chloride was determined in adult albino mice (CFT-Swiss) following administration (intraperitoneal) of single doses. Subsequently, multiple sublethal doses (1.25, 2.5, and 5.0 micromol/100 g of body weight per day for 3 days) were used to characterize effects on testicular histoarchitecture, lipid peroxidation (LPO) in testis (homogenates, microsomal or mitochondrial fractions) and epididymal sperm, DNA damage, induction of apoptosis in testis, and incidence of sperm head abnormalities. Although short-term doses of nickel induced only a minimal LPO response, multiple doses elicited a moderate (15% to 30%) increase in LPO in whole homogenates and higher dose-related increases in both mitochondrial (20% to 50%) and microsomal fractions (25% to 60%). This was associated with a significant increase in DNA damage in the testis as evidenced by increased single-strand breaks (fluorimetric analysis of DNA unwinding assay). Further, at higher doses, nickel-induced apoptosis was demonstrable in the testis biochemically. Although caudal sperm counts determined at all sampling weeks showed no alterations, analysis for head abnormalities revealed a nearly 3- to 4-fold increase in the percentage of abnormal sperms among the nickel-treated males during the first 3 weeks. Furthermore, mating of nickel-treated (2.5 micromol/100 g of body weight per day for 5 days) males sequentially for a period of 5 weeks with untreated females resulted in a significant increase in male-mediated dominant lethal-type mutations (the frequency of dead implantations) during the first 3 weeks, suggesting a stage-specific effect on postmeiotic germ cells. These findings suggest that testicular toxicity of nickel compounds may be related to enhanced production of reactive oxygen species, probably mediated through oxidative damage to macromolecules, including damage to DNA.     

Skin substitutes in the treatment of deep partial skin thickness burns in children: clinical experience and long-term results

This report describes the use of skin substitutes in the treatment of deep partial skin thickness burns in childhood. These are lesions that, if treated inadequately, can result in severe scarring. However, if treated appropriately, they can heal without any sequelae, which is obviously crucial for aesthetic and psychological reasons. This review contains children admitted to the authors' Burn Unit over a 5-year period (1984-88) with deep partial skin thickness lesions which were treated with synthetic and/or biosynthetic skin substitutes and without surgical procedures. This group of children has been compared with another group hospitalized for burns of the same depth and treated with conventional closed wound management. First, short-term results are presented, highlighting healing time, followed by the long-term results from an aesthetic and functional viewpoint.     

European comparative clinical study of Inerpan: a new wound dressing in treatment of partial skin thickness burns.

Eleven European burns centres in five countries (Belgium, England, Germany, Italy, Switzerland) participated in a prospective, randomized clinical trial comparing a new wound dressing Inerpan with conventional dressings such as petroleum jelly gauze, petroleum jelly gauze with antibiotics and silver sulphadiazine cream. The indication was partial skin thickness burns and 62 patients were included. In each patient, two similar lesions (with respect to depth and surface area) were compared, one being treated with Inerpan, the other one with a control dressing. The following parameters were studied: healing time, quality of healing, intensity of pain, local tolerance and frequency of dressing changes. Analysis of the results showed that Inerpan-treated sites healed faster than conventional ones, and were associated with a highly significant reduction of pain. The frequency of dressing changes was greatly reduced and the local tolerance was good.     

Use of skin allograft and its donation rate in Singapore: an 11-year retrospective review for burns treatment

An 11-year retrospective review (1993 to 2003) of 102 severe burn patients (>40% total body surface area and undergone wound excision surgery) was performed to determine the efficacy of early wound debridement and coverage of large burns with skin allografts, a treatment introduced here in 1998 with the establishment of a skin banking facility. While there was no significant reduction in mortality, length of hospital stay decreased by 15.7 days (P < .05) during the post-skin-banking period. Skin allograft donation rates from multiorgan donors were consistently fewer compared with corneal donation, mainly due to strong cultural beliefs and public misconceptions regarding skin harvesting. The overall tissue donation rate in Singapore may improve if efforts focus on deceased cases sent to the state coroner where retrieval and counseling can be centralized.     

Scalding in Turkish children: comparison of burns caused by hot water and hot milk

INTRODUCTION: Our aim in this study was to compare the clinical differences and etiologic risk factors for hot water and hot milk scald burns in Turkish children. METHODS: The retrospective study examined the cases of 140 children aged 0.1-7 years who had scald burns treated in three burn units of a Turkish hospital network between March 2000 and December 2004. The patients were categorized in two groups: hot water burns or hot milk burns. RESULTS: Ninety-five (67.9%) patients had hot water burns and 45 (47.1%) had hot milk burns. The proportion of patients with hot milk burns who lived in rural areas was significantly higher than the corresponding proportion for the hot water cases (75.6% versus 52.6%, respectively; p<0.01). In 20 (44%) of the hot milk cases, the burn was caused by milk being boiled in large pots outdoors for cheese production. The other 25 hot milk cases were caused by milk being boiled in the kitchen. The mean (+/-S.D.) percentage total body surface area burned in the hot milk cases was higher than that in the hot water cases (33.6+/-2.24% versus 21.42+/-1.43%, respectively; p<0.001), and the corresponding mean percentages of TBSA with full-thickness burns were 9.2+/-2.52% versus 3.13+/-0.83%, respectively; (p=0.083). The mean percentages of TBSA with second-degree burns showed the same trend (29.0+/-12.39% versus 18.8+/-1.47%, respectively; p<0.001) higher percentage of the children with hot milk burns required antibiotics (78% versus 52.8%, respectively; p<0.006). Seven (7.4%) of the hot water burn patients and 15 (33.3%) of the hot milk burn patients died during the study period (p=0.025; overall mortality rate 15.7%). CONCLUSION: Children scalded with hot milk tend to have more extensive burns, and thus have higher mortality, than those scalded with hot water. To create effective programs for preventing scald injuries in Turkey and elsewhere, it is essential to consider ethnic and cultural issues based on these characteristics. Simple precautions should be explained and methods of using liquids such as hot milk should be researched in different geographic locations in order to formulate good prevention strategies.     

Melasma and low-energy Q-switched laser: treatment assessment by means of in vivo confocal microscopy

Melasma is an acquired disorder of pigmentation for which several therapeutical options are currently available. Among them, low-energy Q-switched Nd:YAG laser (1,064 nm) has been successfully applied in case series although its long-term efficacy has yet to be proven. In vivo confocal microscopy is a novel imaging technique that permits to explore the skin tissue at a nearly histologic resolution. The aim of our study was to evaluate the laser treatment efficacy by means of confocal microscopy at different time points to elucidate the mechanism of action of the laser and its possible drawbacks. Eight women who presented with melasma on the face were subjected to low-energy Q-switched Nd:YAG laser treatment and then analyzed by means of confocal microscopy. An overall improvement of melasma was noticed clinically and microscopically by means of confocal microscopy. Four cases revealed the presence of dendritic-shaped cells upon confocal microscopy and those patients were the ones presenting with a relapse of the disease. The interpretation of these cells is that they could represent reasonably activated melanocytes. This opens the question whether laser treatment should be modulated to avoid side-effects associated with its use. Confocal microscopy has emerged as an excellent tool for a better understanding of the changes occurring during laser treatment.     

Efficacy of hydrosurgical excision combined with skin grafting in the treatment of deep partial-thickness and full-thickness burns: A two-year retrospective study

IntroductionDeep partial-thickness and full-thickness burn wounds often undergo tangential excision or escharectomy to expose healthy tissue, combined with skin grafting to promote wound healing. However, conventional tangential excision with the humby knife leads to inevitable damage to the dermis while excising burn tissue due to the lack of precision. Indeed, the preservation of dermal tissue is a key factor in determining wound healing and scar quality. The precision and tissue selectivity of the Versajet Hydrosurgical System has been established for excising burn tissue while preserving dermal tissue. In this study, we retrospectively compared the efficacy of "Hydrosurgical excision combined with skin grafting" and "Conventional tangential excision combined with skin grafting" in treating deep partial-thickness and full-thickness burn wounds to demonstrate that hydrosurgery improved the treatment of deep partial-thickness and full-thickness burns.MethodsA total of 86 patients with deep partial-thickness and/or full-thickness burns with a total burn surface area (TBSA) ≤ 25% from July 2018 to July 2020 were included in this study and were divided into experimental (hydrosurgical excision combined with skin grafting, n = 43) and control (conventional tangential excision combined with skin grafting, n = 43) groups. Parameters were analyzed, including the intraoperative blood loss volume per unit area of grafted skin, surgery duration, wound healing time, skin graft survival, and the treatment costs per unit of burned area. Scar assessment was performed at 1 year with the modified Vancouver Scar Scale linked with TBSA (mVSS-TBSA).ResultNo significant difference was found in male to female ratio, age, weight, TBSA, burn depth, skin grafting area (SKA), skin grafting methods, cases treated with carbon dioxide fractional laser or incidence of inhalation injury, and the incidence of hypovolemic shock between two groups(p > 0.05). Compared with the control group, patients treated with hydrosurgical excision combined with skin grafting experienced less intraoperative blood loss volume per unit area of grafted skin (p < 0.05). The mVSS-TBSA of patients that underwent hydrosurgical excision combined with skin grafting was significantly improved in comparison to the control group (p < 0.01). No significant difference was found in surgery duration, wound healing time, skin graft survival and treatment costs per unit of burned area between the two groups (p > 0.05).ConclusionHydrosurgical excision combined with skin grafting reduced intraoperative blood loss volume per unit area of grafted skin, improved scarring 1-year after injury, and did not increase the treatment costs per unit of burned area. This technique provides a novel alternative for managing deep partial-thickness and full-thickness burn wounds.