Skin Lesions In Rats Research Articles

Attenuation of 1-chloro-2,4-dinitrobenzene-induced inflammation in atopic dermatitis-like skin lesions in rats by a pyrrole containing FELL-NH 2 bioconjugate: Cannabinoid receptor type 1 involvement

Atopic dermatitis (AD) is a chronic inflammatory skin condition of significant health and social importance, which justifies the search for new means of treatment. Since the endogenous cannabinoid system appears to be involved in the pathogenesis of AD, the proposed article summarizes the clinical impact on skin inflammation in a rat model of 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis-like condition after exogenous systemic administration of the cannabinoid receptor type 1 (CB1r) agonist anandamide, as well as after local treatment with a newly synthesized pyrrole moiety containing bioconjugate of FELL tetrapeptide with CB1r-dependent analgesic activity. The changes in skin lesions and ear thickness were estimated along with the CB1r expression immunohistochemically determined on skin punch biopsies. The results showed attenuation of skin lesions by anandamide and lack of positive effect after introduction of CB1r antagonist, accompanied by a change in CB1r expression, suggesting the involvement of the cannabinoid system in the defensive functions of the skin. The topically applied newly synthesized bioconjugate also favorably affected skin manifestations of inflammation, but without a change in CB1r expression, suggesting the involvement of other mechanisms in the reported effects.

СОЧЕТАННОЕ ПРИМЕНЕНИЕ ХИРУРГИЧЕСКОГО ИССЕЧЕНИЯ ЛУЧЕВОЙ ЯЗВЫ И ТРАНСПЛАНТАЦИИ СИНГЕННЫХ КЛЕТОК СТРОМАЛЬНО-ВАСКУЛЯРНОЙ ФРАКЦИИ ЖИРОВОЙ ТКАНИ ПРИ ЛЕЧЕНИИ ТЯЖЕЛЫХ МЕСТНЫХ РАДИАЦИОННЫХ ПОРАЖЕНИЙ В ЭКСПЕРИМЕНТЕ

Purpose: To study the therapeutic efficacy of the combined use of surgical excision of radiation ulcers and transplantation of syngeneic cells of the stromal-vascular fraction (SVF) of adipose tissue in the treatment of severe local radiation lesions. Material and methods: Experiments were conducted on rats males of the inbred line Wista‒Kyoto weighing 230‒250 g. Animals were irradiated on an X-ray unit locally in the iliac-lumbar region of the back at a dose of 110 Gy (voltage on the tube 30 kV, current strength 6.1 mA, filter 0.1 mm Al), at a dose rate of 20,0 Gy/min. Irradiation field area 8.2 cm2. Radiation exposure made it possible to obtain severe skin lesions in rats with long-term non-healing ulcers, and without critical radiation exposure to the underlying tissues. Morphological study showed that the area of skin necrosis (with a maximum in the center of the irradiation zone) was formed by 21‒23 days after irradiation and was characterized by the presence of pronounced changes in all layers of the skin. Surgical excision of radiation ulcers was performed on 22 days after exposure to radiation. The affected tissue was removed to the entire depth of the skin up to the fascia of skeletal muscles. Excision of the skin was carried out, retreating 6‒8 mm from the outer border of the radiation ulcer. Cell transplantation was carried out twice 5 and 12 days after excision of the ulcer. SVF cells were obtained from intact animals from subcutaneous adipose tissue treated with trypsin. A suspension of SVF cells of adipose tissue in 1 ml of a sterile Solution of Henks was injected under the skin at 5 points around the excision zone, retreating 5‒7 mm from the edge of the focus. The number of injected cells in one transplant was 2.5×106. Results: The area of radiation ulcers in rats of the control group in the period from 27 to 105 days after irradiation slowly decreased from 2.8±0.2 cm2 to 1.2 ± 0.2 cm2. Excision of radiation ulcers led to rapid complete visible healing of the wound defect (already by 70 days after irradiation) with the formation of atrophic scars. Transplantation of SVF syngeneic cells increased the rate of healing of the surgical wound. Conclusion: The results show that surgical excision of radiation ulcers in combination with cell therapy may be an effective way to treat severe local radiation lesions.

Examination of skin lesions in rats with induced hyperthyroidism and hypothyroidism

ABSTRACT We investigated the pathogenesis of skin lesions due to hypothyroidism and hyperthyroidism in rats. We used 30 rats allocated into hypothyroidism, hyperthyroidism and control groups. Blood samples were evaluated for levels of thyroid stimulating hormone (TSH), tri-iodothyronine (T3) and thyroxine (T4). Skin samples were examined for melan-A, lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1), cluster of differentiation 31 (CD31), protein gene product 9.5 (PGP9.5), calretinin, chromogranin, synaptophysin and pancytokeratin. Histopathological examination of the skin sections revealed thickened epidermis in the hyperthyroidism group due to an increased number of cells, and a decreased number of hair follicles and epithelial cell rows in the epidermis with an increased number of fat cells in the dermis of the rats in the hypothyroidism group. No significant difference was observed in the immunoreactions of pancytokeratin, PGP9.5, CD31 and synaptophysin among the groups. The hyperthyroidism and hypothyroidism groups exhibited a marked increase in melan-A immunoreaction. Expression of LYVE-1, chromogranin and calretinin was increased in the hyperthyroidism group and decreased in the hypothyroidism group. We found that melan-A, LYVE-1, chromogenin and calretinin play an important role in the pathogenesis of skin lesions caused by thyroid disorders.

<i>In vitro</i> enzyme activity and <i>in vivo</i> healing activity of the protein extract from pineapple peel

The pineapple is a fruit that has wide acceptance worldwide both in natural form, as industrialized. Your peel is a residue generated by food industries and from this residue can obtain a protein extract which is a good source of bromelain. This study aimed to obtain a protein extract from pineapple peel, evaluate its enzyme activity and its healing properties in skin lesions in rats. Seven animal groups were used: control, treated with 5% of protein extract, 10% of protein extract and pure protein extract; 5% of commercial bromelain, 10% of commercial bromelain and pure commercial bromelain. The animals were subjected to a tissue incision and treated for 21 days. Proteolytic and specific activities of the protein extract were 1.30 U mg -1 and 45 x 10 -3 U µg -1 and, for commercial bromelain, 1.04 U mg -1 and 6 x 10 -3 U µg -1 , respectively. In the histology of the lesion, there was no significant difference between the control and treated groups; however, macroscopically, the prepared topical formulations assisted in the recovery of skin lesions, providing a significant reduction in their width, in the groups treated with pure protein extract, 5 and 10% commercial bromelain, and pure bromelain.

Boosting Angiogenesis in Skin Mechanical Trauma Area by means of Neoskin Skin-Substitute Preparation

Various skin-replacements nowadays are widely used alongside other up-to-date methods for treatment of skin wounds for using this technique decreases the need for wound vascularization, increases the wound’s skin component, decreases or completely removes inhibitory factors, decreases inflammatory process thus contributing to quick and safe wound’s covering up ensuring tissue reparation flexibility. The goal of the study was to assess the influence of Neoskin skin-replacement upon angiogenesis and wound reparation intensity in experiment involving white rats. Skin wound was modeled by removing a 4,9 square mm skin flap by means of incision under general narcosis (Zoletil). The treatment of the wound included the application of innovation preparation Neoskin produced by “Trans-Technologies”, Russia upon the skin wound for 14 days. The preparation Neoskin is a three-layer matrix consisting of extracellular matrix proteins and mesenchimal cells. Angiogenesis markers concentrations were determined in blood plasma by means of immune-enzyme assay (VEGF, NO, tPA and PAI-1). Vascular network density in the wound surface zone was determined by means of histological method in slides stained with hemotoxillin-eosine with the aid of light-microscopy in 50 fields of vision. Skin mechanical trauma model not involving subjacent organs and tissues was accompanied by angiogenesis changes characteristic of wound healing process. Transitory reduction of microcirculatory network density in the area of the wound and increasing activity of basic proangiogenic factors necessary for reparation took place. The use of Neoskin in the therapy of skin lesions in rats has contributed to fast activation of angiogenesis and wound healing.

Biocompatibility of Pegylated Fibrinogen and Its Effect on Healing of Full-Thickness Skin Defects: A Preliminary Study in Rats

Introduction: A synthetic polymer polyethylene glycol (PEG), was conjugated to fibrinogen as a threedimensional and biodegradable skin wound dressing matrix. This PEG-fibrinogen (PEG-fib) was tested in vivo in a skin wound time course study for its biocompatibility and biodegradation, after being delivered into the wound by injection and polymerized in situ by photo-activation. Materials and methods: The nature of the inflammatory response to the implanted material in acute, 8 mm diameter, full-thickness skin lesions in rats was histologically evaluated at 7 days (n=6) and 14 days (n=6). Six wounds per time point were left untreated as controls. Results: After 14 days, wounds of both groups were healed by up to 78% contraction and 22% epithelialization. Immune cells such as foreign body giant cells, macrophages, plasma cells and lymphocytes were seen in the PEGfib treated wounds at both time points, however in low numbers and similar to controls. The amount of immune cells dropped between day 7 and 14. Remnants of the gel were found at day 7 in two of the PEG-fib treated wounds, no PEG-fib were found after 14 days in any of the wounds. There was no difference in epithelialization between the two treatments at both time points. Discussion: The histological evaluation showed good biocompatibility of the PEG-fib, such that a foreign body reaction to the implant could be ruled out. The amount of immune cells was in accordance to a normal reaction to an implanted resorbable biomaterial. Conclusion: The PEG-fib hydrogel is fully biocompatible as a skin wound dressing. It provides initial moisture to the wound bed and is gradually resorbed and replaced by structured skin tissue. An attractive future perspective would be to prepopulate the PEG-fib hydrogel with cells (e.g. fibroblasts), or load it with growth factors or other soluble mediators to further promote healing of complicated skin wounds.

A ação do óleo de pequi (Caryocar brasiliense) no processo cicatricial de lesões cutâneas em ratos.

RESUMO O objetivo deste estudo foi analisar o efeito do óleo de pequi no processo cicatricial de lesões cutâneas em ratos. A pesquisa foi iniciada após a provação da CEUA- FACID sob o nº de protocolo 005/12 e obedeceu aos princípios éticos da experimentação animal de acordo com a Lei Federal nº 11.794/2008. Foram utilizados 20 ratos machos, Wistar (Rattusnorvegicus), peso corpóreo de 300-350g, divididos aleatoriamente em dois grupos iguais: GI- controle (C); GII- tratado com óleo de pequi (T). Cada grupo foi dividido em dois subgrupos, de cinco animais cada, conforme os tempos experimentais estudados de 7(A) e 14(B) dias. Após anestesia e antissepsia foi produzida cirurgicamente ferida circular de 2,5 cm de diâmetro na região dorso lombar do animal. Os animais do Grupo II foram tratados com aplicação tópica diária de 1 ml do óleo de pequi, respeitando os tempos experimentais descritos. Concomitante à mensuração da área da lesão, os ratos foram eutanasiados para realização do processamento histológico e análise do percentual de regressão das lesões. No grupo GII nos diferentes tempos experimentais de 7 e 14 dias foi observado maior percentual de regressão das lesões em relação ao GI (p < 0,05). A partir da análise histológica foi possível detectar que no GII houve menor número de células inflamatórias e maior número de fibroblastos em relação ao GI nos diferentes tempos experimentais (p < 0,001). Conclui-se que o uso do óleo de pequi apresentou influência positiva no processo de reparo de lesões cutâneas em ratos, por promover maior velocidade do reparo tecidual, fato evidenciado pelo fechamento mais rápido das feridas e observação de características inflamatórias reduzidas no grupo tratado em relação ao grupo controle, sugerindo que a inflamação pode já ter regredido no grupo tratado.

Cenostigma macrophyllum Tul. on the healing of skin wounds in rats with Diabetes mellitus

To investigate the effect of Cenostigma macrophyllum Tul. in the tissue repair process of skin lesions in rats with induced Diabetes mellitus. Sixty-three male Wistar rats were distributed into three groups: control (C), diabetic (D), and diabetic treated with an oil-in-water emulsion of the plant (DPL) subdivided according to time of observation (seven, 14, and 28 days). Diabetes was induced by administration of by injection of streptozotocin (50 mg/kg, after a 12-h fast) into the penile vein and confirmed by glucose levels exceeding 240 mg/dL. Held surgical lesion (2.5 cm in diameter) on the back of the animals. The DPL received topical application of group of the oil-in-water emulsion plant (0.5 ml). To evaluate the levels of nitric oxide, was collected 5 ml of blood from the abdominal aorta, after his euthanasia. The samples of interest were sent for routine histological processing. A reduction in the percentage of inflammatory cells and increased numbers of fibroblasts in the group DPL, seven days, compared to the other groups. At 14 days, the DPL group also showed a higher concentration of nitric oxide (p<0.01) than in groups C and D. The oil-in-water emulsion of C. macrophyllum Tul accelerated wound healing in diabetic rats.

Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions

Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many types of human cancer. BRAF mutations that constitutively activate MAPK signalling and bypass the need for upstream stimuli occur with high prevalence in melanoma, colorectal carcinoma, ovarian cancer, papillary thyroid carcinoma, and cholangiocarcinoma. In this report we characterize the novel, potent, and selective BRAF inhibitor, dabrafenib (GSK2118436). Cellular inhibition of BRAFV600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death. In a BRAFV600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors. In addressing this issue, we showed that concomitant administration of BRAF and MEK inhibitors abrogated paradoxical BRAF inhibitor-induced MAPK signalling in cells, reduced the occurrence of skin lesions in rats, and enhanced the inhibition of human tumor xenograft growth in mouse models. Taken together, our findings offer preclinical proof of concept for dabrafenib as a specific and highly efficacious BRAF inhibitor and provide evidence for its potential clinical benefits when used in combination with a MEK inhibitor.

Ornithodoros brasiliensis (mouro tick) salivary gland homogenates inhibit in vivo wound healing and in vitro endothelial cell proliferation

Ornithodoros brasiliensis is a nidicolous tick only found in the southern Brazilian highlands region. O. brasiliensis parasitism is frequently associated with toxicosis syndrome, which can lead to severe reactions, ranging from local pruritus and pain to systemic disturbances both in humans and dogs. One of the most frequent findings associated with an O. brasiliensis bite is a slow healing lesion at the site of tick attachment, which can take several weeks to heal. This work tested the hypothesis that an O. brasiliensis salivary gland homogenate is able to modulate the skin wound-healing process in vivo, using a model of excisional skin lesion in rats, which are divided into two groups: (1) control group and (2) treated group, which topically received salivary gland homogenate equivalent to the protein amount of one whole salivary gland (≈5 μg protein). The hypothesis that O. brasiliensis salivary gland homogenates interfere with endothelial cell proliferation, a key role phenomenon in wound healing, was also tested. O. brasiliensis salivary gland homogenates significantly delay skin wound healing. The time to full healing of skin lesions in control rats was 15 days, contrasting with 24 days in rats topically treated with O. brasiliensis salivary gland homogenates. The calculated HT50 (healing time to recover 50% of the wound area) for control groups was 3.6 days (95% CI, 3.2-3.9) and for salivary gland treated rats was 7.7 days (95% CI, 7.0-8.4). Salivary gland homogenates have a strong cytotoxic activity on cultured endothelial cells (LC50, 13.6 mg/ml). Also, at sublethal concentrations (≤3 mg/ml), salivary gland homogenates have a remarkable anti-proliferative activity (IC50 0.7 mg/ml) on endothelial cells, equivalent to ≈0.03 salivary gland pairs, an activity which seems to be much greater than reported for any other tick species. This is the first report about the biological activities of O. brasiliensis salivary compounds and provides the first in vivo evidence to support the concept of wound-healing modulation by tick salivary secretions. Results shown here contribute to an understanding of O. brasiliensis tick toxicosis syndrome, and also increase our knowledge of tick salivary bioactive compounds.

Hydrogels containing rutin intended for cutaneous administration: efficacy in wound healing in rats

Objective: Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats.Methods: Hydrogels were prepared using Carbopol Ultrez® 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress.Results and discussion: Hydrogels showed adequate pH values (5.50–6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels.Conclusion: This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing.

The Role of Residual Gadolinium in the Induction of Nephrogenic Systemic Fibrosis-Like Skin Lesions in Rats

Nephrogenic systemic fibrosis (NSF) is an acquired, idiopathic disorder. Most of the cases are observed in patients with end stage renal disease (ESRD). The objective of this nonclinical animal study was to test the hypothesis that gadolinium (Gd) deposits play a role in the induction of NSF lesions. In addition, we evaluated whether an acute response to Gd exposure can initiate a process that results in fibrosis of the skin. Han-Wistar rats were administered 3 intravenous injections of Gd-DTPA-BMA formulated without Gd-free excess ligand (Gadodiamide without Caldiamide) at a dose of 2.5 mmol/kg of body weight (b.w.) per injection given at 24-hour or 14-, 28-, or 56-day intervals. The occurrence and development of NSF-like fibrosing dermopathy lesions were followed. The Gd concentration was determined by Inductively Coupled Plasma Mass Spectrometry in skin biopsies taken during the study and organ samples taken at the end of the study.In a separate study, after injection of a single intravenous dose of 2.5 mmol/kg b.w. Gd-DTPA-BMA administered to Han-Wistar rats, the expression of cytokines and signaling molecules in serum and skin tissue was determined by quantitative RT-PCR and Luminex technology 6 hours or 14, 28, or 56 days. The occurrence of NSF-like macroscopic skin lesions differed between the injection groups. Shorter injection intervals resulted in more severe skin reactions. In contrast, the injection interval did not influence the long-term presence and level of accumulation of Gd concentration in tissue. The single injection of Gd-DTPA-BMA was followed by a rapid and transient induction of signaling molecules in the serum (MCP1, MCP3, IL1, IP-10, Osteopontine SCF and Timp1) as well as in the skin (MCP1 and TGFb). The presence of NSF-like fibrosing dermopathy in rats was found to be dependent on the injection interval and not on the amount of Gd in tissue. Our findings suggest the possibility of a more acute intrinsic reaction on administration of Gd-DTPA-BMA that triggers events leading to the development of skin lesions. The finding that single injections of Gd-DTPA-BMA were accompanied by a fast and transient induction of signaling molecules that are known to be involved in several fibrotic events provides additional support for this hypothesis. The study findings, however, do not support the theory that the long-term presence of Gd plays a relevant role in the development of NSF.

Prolactin and its role in wound healing

Wound healing is an extremely complex process involving different cell-types and also growth factors, cytokines and components of the extracellular matrix. Each phase of wound healing is characterized by closely integrated events thanks to mechanisms that involve chemotaxis of specific cell-types and release of molecules that act as paracrine effectors; even though today it can also refer to endocrine effectors, in fact the existence of numerous and complex interactions between endocrine and immune system is now well known. One of these interactions is that with a peptide hormone secreted by the anterior hypophysis: prolactin (PRL). PRL is a potent immunomodulator capable of undertaking a specific role in regulating the immune response both humoral and cell-mediated one. In recent years, a lot of evidences indicate that several other tissues are able to produce PRL. It is believed that PRL expression in skin can probably be related to an inflammatory response and may play a role in the wound healing process. From these considerations, our second experience, here described, which aims to assess PRL topic treatment effects on wound healing of skin lesions in rats, began. In our study, PRL treatment have been made by dripping on lesions produced on the back of each animal, using the following protocol: control group (100 µl of PBS); experimental group (100 µl of PRL 2 ng/ml in PBS). Total results of our studies, including this one that shows a greater rate of wound healing in PRL-treated animals, support the idea of a crucial role of PRL on wound healing in relation to its effects both on angiogenesis and proliferation of keratinocytes in the re-epithelialization process, taking to restored skin.

Efficacy and safety of lanthanoids as X-ray contrast agents

Objective It has been suggested that elements from the lanthanoid (Ln) series may be well suited for use as absorbing elements in X-ray contrast agents (CA). Because gadolinium, an element of the lanthanoid series, has been identified as being possibly associated with nephrogenic systemic fibrosis (NSF), a rare but potentially severe disease, we sought to determine if other lanthanoids might possess a similar potential. Materials and methods By computed tomography (CT), we compared the X-ray attenuation of all lanthanoids to that of iodine in vitro. In addition, we injected Han-Wistar rats on five consecutive days with 2.5 mmol Ln/kg bodyweight intravenously to test several Ln–DTPA–BMA complexes (praseodymium, europium, gadolinium, and holmium). Saline solution and a Ca–DTPA–BMA group served as controls. Ln concentrations in the skin and organs were determined by inductively coupled plasma mass spectrometry (ICP-MS). This method measures the total Ln content and cannot differentiate between chelated and unchelated Ln. In addition, serum cytokine levels were measured by Luminex technology. The complex stability of the Ln–DTPA–BMA complexes was also assessed in vitro. Results Lanthanoids showed up to 50% higher X-ray attenuation than iodine in CT. The highest X-ray attenuation was observed with holmium and erbium. Differences in the in vitro complex stability of Pr–, Eu–, Gd–, and Ho–DTPA–BMA complexes were observed. The complex stability differences were also reflected by differences in the concentrations in tissue of the lanthanoids in vivo. Injections of Ln complexes caused NSF-like skin lesions in rats and a rapid upregulation of pro-fibrotic and inflammatory serum cytokines. The Ca–DTPA–BMA complex did not to induce pro-fibrotic cytokines or skin lesions. Pr-DTPA-BMA appeared to be toxic; all Pr-DTPA-BMA treated animals died within the first four days of the experiment and were therefore excluded from further analyses. Conclusion Lanthanoids are very well suited for higher X-ray tube voltages, particularly CT examinations. However, Ln-specific induction of NSF-like skin lesions and rapid elevation of pro-fibrotic serum cytokines levels were observed in rats following multiple administrations of high doses of Ln-DTPA-BMA complexes. The results of this animal study suggest that the stability of lanthanoid complexes may be an important consideration in evaluating the potential for in vivo safety. Furthermore the results suggest a potential of the entire class of lanthanoids to have the potential to trigger NSF-like skin lesions in rats rather than only some of the specific elements of this series.

Effects of a single near-infrared laser treatment on cutaneous wound healing: Biometrical and histological study in rats

Background Low intensity laser therapy has been recommended to support the cutaneous repair; however, so far studies do not have evaluated the tissue response following a single laser treatment. This study investigated the effect of a single laser irradiation on the healing of full-thickness skin lesions in rats. Methods Forty-eight male rats were randomly divided into three groups. One surgical lesion was created on the back of rats using a punch of 8 mm in diameter. One group was not submitted to any treatment after surgery and it was used as control. Two energy doses from an 830-nm near-infrared diode laser were used immediately post-wounding: 1.3 J cm −2 and 3 J cm −2. The laser intensity 53 mW cm −2 was kept for both groups. Biometrical and histological analyses were accomplished at days 3, 7 and 14 post-wounding. Results Irradiated lesions presented a more advanced healing process than control group. The dose of 1.3 J cm −2 leaded to better results. Lesions of the group irradiated with 1.3 J cm −2 presented faster lesion contraction showing quicker re-epithelization and reformed connective tissue with more organized collagen fibers. Conclusions Low-intensity laser therapy may accelerate cutaneous wound healing in a rat model even if a single laser treatment is performed. This finding might broaden current treatment regimens.

Avaliação do uso do extrato bruto de Jatropha gossypiifolia L. na cicatrização de feridas cutâneas em ratos

Phytotherapy is one of the research branches in the healing process of surgical wounds. To analyze the morphological aspects of the healing process occurring in open skin lesions in rats under administration of raw extract from Jatropha Gossypiifolia L. Sixty Wistar rats were utilized. A 2 cm wound in diameter was done in each animal at the dorsal region. The animals were divided into two groups, each one consisting of 30 animals. Each group was subdivided into three subgroups of ten. They were analyzed in the 7th, 14th and 21st post-operative day. The two groups were compared through macroscopic analysis using digital planigraphy and histological examination. The microscopic parameters considered were the vascular proliferation, polymorph and mononuclear cells, fibroblastic proliferation, collagen and epithelium formation. Epithelization occurred in a same amount in all animals. There was no chronic inflammation on 21st day in the Jatropha group and also no difference in polymorphonuclear cells between the groups. The fibroblastic reaction was better on the 7th day in the Jatropha group and equal in the remaining ones. Colagenization was greater on 7th and 14th days in Jatropha and better re-epithelization occurred in the same group in the 7th day. Although with histologic aspects favoring the Jatropha, no significant differences concerning to the macroscopic and microscopic aspects were observed among the skin wounds receiving raw extract Jatropha and those that received no treatment in the final evaluation.

Effects of topical antiinflammatory agents on Freund's adjuvant-induced skin lesions in rats.

Freund's adjuvant, when administered intradermally to rats, causes polyarthritis as well as inflammation of the skin, eye, gastrointestinal and genitourinary tracts. We assessed the effects of antiinflammatory drugs on ear skin lesions to determine if this might be a useful skin inflammation model. The hind paw of male Lewis rats was injected with Mycobacterium butyricum in paraffin oil. Lesions appeared between days 13 and 15 after adjuvant injection. Each ear exhibited on average 1 to 3 highly erythematous, elevated lesions, 2 to 3 mm in diameter. By histology, the lesions consisted of epidermal hyperplasia, with a prominent accumulation of inflammatory cells in the dermis. Ears were treated topically with glucocorticoids, cyclosporine and indomethacin on days 15 through 21 after adjuvant injection. By day 22, dexamethasone, fluocinolone acetonide, and cyclosporine caused near-complete clearing of lesions whereas indomethacin exacerbated the inflammation by causing increased numbers of skin lesions. These results show the potential usefulness of adjuvant-induced skin lesions in rats as a novel subchronic inflammation model.

Collagen prolyl hydroxylase inhibitor and reduced collagen formation in cotton pellet-induced granuloma and skin wound healing in rats.

P-1894B an inhibitor of collagen prolyl hydroxylase was applied topically to cotton pellet-induced granuloma and to skin lesions in rats. The total hydroxyproline content of the granulomata was significantly reduced by this agent. It also reduced the hydroxyproline content in the tissues surrounding skin lesions during the healing process, with delayed diminution in lesion size. These results suggest that collagen prolyl hydroxylase inhibitor P-1894B may be a suitable agent for topical treatment of hypertrophic scar tissue or keloid.