Comparative experimental study of wound healing in mice: Pelnac versus Integra.

Strategies for skin regeneration have been developed to provide effective treatment for cutaneous wounds and disease. Dermal substitutes have been used to cover the lesion to facilitate cell colonization, thereby promoting dermal regeneration. However, very little is known about Pelnac matrix especially at histological level. Therefore, the present work carried out an experimental in vivo comparative analysis between Pelnac and Integra, the most used dermal templates, in a mouse model of full-thickness skin wounds. Histological sections performed at the 3rd, 6th and 9th days after surgery were analyzed with regard to inflammatory response and vascularization. Both templates were completely incorporated in all animals at the end of the analyzed period. Pelnac-treated animals displayed reduced granulation tissue during the first 6 days of treatment compared to the animals treated with Integra at the same time period. The number of inflammatory cells (neutrophils) was similar in both groups during the period, significantly reducing at the end of inflammatory phase (9th day of treatment) consistent with the progression of healing process. In addition, the density of blood vessels was also statistically similar in both matrices. Therefore, the two dermal templates displayed comparable biological behavior in tissue repair. It is noteworthy that this is the first experimental study comparing Pelnac and Integra dermal templates with focus on full-thickness skin wounds.

Dermoscopic features of thin melanomas: a comparative study of melanoma in situ and invasive melanomas smaller than or equal to 1mm.

BACKGROUND: Dermoscopy allows the early detection of melanomas. The preoperative determination of Breslow index by dermoscopy could be useful in planning the surgical approach and in selecting patients for sentinel lymph node biopsy. OBJECTIVES: This study aims at describing the dermoscopic features of thin melanomas and comparing melanomas in situ with invasive melanomas less than or equal to 1 mm thick. METHODS: This was an observational retrospective study in which the dermoscopy photographs of 41 thin melanomas were evaluated. Three observers evaluated together 14 dermoscopic criteria. RESULTS: Among thin melanomas, the most frequent criteria were presence of asymmetry in two axes in 95% of cases (39 cases), 3 or more colors in 80.4% of cases (33 cases), atypical dots or globules in 58.5% of cases (24 cases) and atypical network or streaks in 53.6% of cases (22 cases). The group of invasive melanomas presented with a higher frequency and statistical significance (p <0.05) 3 or more colors (OR: 16.1), milky red areas (OR: 4.8) and blue-white veil (OR: 20.4), and a greater tendency to have streaks or atypical network (OR: 3.66). CONCLUSIONS: Thin melanomas tend to have asymmetry in the two axes, 3 or more colors, atypical dots or globules and atypical network or streaks. Melanomas in situ tend to have up to 2 colors, no blue-white veil and no milky red area. Invasive melanomas tend to have 3 or more colors, a milky red area, blue-white veil, and atypical network or streaks. Further studies are needed to confirm these findings.

Dermoscopic features of thin melanomas: a comparative study of melanoma in situ and invasive melanomas smaller than or equal to 1mm / Caracteristicas dermatoscopicas de melanomas finos: estudo comparativo entre melanomas in situ e melanomas invasivos menores ou iguais a 1mm

BACKGROUND: Dermoscopy allows the early detection of melanomas. The preoperative determination of Breslow index by dermoscopy could be useful in planning the surgical approach and in selecting patients for sentinel lymph node biopsy. OBJECTIVES: This study aims at describing the dermoscopic features of thin melanomas and comparing melanomas in situ with invasive melanomas less than or equal to 1 mm thick. METHODS: This was an observational retrospective study in which the dermoscopy photographs of 41 thin melanomas were evaluated. Three observers evaluated together 14 dermoscopic criteria. RESULTS: Among thin melanomas, the most frequent criteria were presence of asymmetry in two axes in 95% of cases (39 cases), 3 or more colors in 80.4% of cases (33 cases), atypical dots or globules in 58.5% of cases (24 cases) and atypical network or streaks in 53.6% of cases (22 cases). The group of invasive melanomas presented with a higher frequency and statistical significance (p <0.05) 3 or more colors (OR: 16.1), milky red areas (OR: 4.8) and blue-white veil (OR: 20.4), and a greater tendency to have streaks or atypical network (OR: 3.66). CONCLUSIONS: Thin melanomas tend to have asymmetry in the two axes, 3 or more colors, atypical dots or globules and atypical network or streaks. Melanomas in situ tend to have up to 2 colors, no blue-white veil and no milky red area. Invasive melanomas tend to have 3 or more colors, a milky red area, blue-white veil, and atypical network or streaks. Further studies are needed to confirm these findings. .

FUNDAMENTOS: A dermatoscopia propicia o diagnóstico mais precoce do melanoma. A estimativa préoperatória da espessura de Breslow através da dermatoscopia poderia ser útil no planejamento da conduta cirúrgica e seleção dos pacientes para a biópsia de linfonodo sentinela. OBJETIVOS: Este estudo objetiva descrever as características dermatoscópicas encontradas em melanomas finos e comparar melanomas in situ com melanomas invasivos menores ou iguais a 1 mm. MÉTODOS: Trata-se de estudo observacional, retrospectivo, no qual avaliouse o registro fotográfico da dermatoscopia de 41 melanomas finos. Três observadores avaliaram em conjunto 14 critérios dermatoscópicos. RESULTADOS: Dentre os melanomas finos, os critérios mais encontrados foram: presença de assimetria nos dois eixos em 95% (39 casos), 3 ou mais cores em 80,4% (33 casos), pontos ou glóbulos atípicos em 58,5% (24 casos) e rede atípica ou estrias radiadas em 53,6% (22 casos). O grupo dos melanomas invasivos apresentou com maior frequência e significância estatística (p<0,05) a presença de 3 ou mais cores (OR: 16,1), áreas vermelho-leitosas (OR: 4,8) e véu (OR: 20,4), além de uma maior tendência em apresentar rede atípica ou estrias radiadas (OR: 3,66). CONCLUSÕES: Os melanomas finos tendem a apresentar assimetria nos dois eixos, 3 ou mais cores, pontos ou glóbulos atípicos e rede atípica ou estrias radiadas. Os melanomas in situ tendem a apresentar até 2 cores, ausência de véu e de área vermelho-leitosa. Os melanomas invasivos tendem a exibir 3 cores ou mais, área vermelho-leitosa, véu, rede atípica ou estrias radiadas. Outros estudos são necessários para a confirmação dos achados. .

Pênfigo vegetante induzido por uso de enalapril / Pemphigus vegetans induced by use of enalapril

Pênfigo Vegetante foi primeiramente descrito como uma variante do pênfigo vulgar, em 1876, por Neumann. Em 1889, Hallopeau descreveu um paciente com pústulas e placas vegetantes, e sugeriu ser uma variante do Pênfigo Vegetante de Neumann. Ambos os tipos de pênfigo vegetante são caracterizados pelo desenvolvimento de placas vegetantes, especialmente, em dobras (axila, inguinal, perianal). Os autores apresentam e discutem um caso de Pênfigo Vegetante com uma clínica incomum, com ausência de acometimento de mucosas e áreas de flexão, em paciente idosa, associado ao uso de enalapril como possível desencadeador. Diagnóstico clínico e histológico sugestivos de Pênfigo Vegetante tipo Hallopeau.

Pemphigus Vegetans was first described as a variant of Pemphigus Vulgaris in 1876 by Neumann. In 1889, Hallopeau described a patient with pustules and vegetating plaques, suggesting that it would be a variant of Pemphigus Vegetans of Neumann. Both types of Pemphigus Vegetans are characterized by the development of vegetating plaques especially on skin folds (axillae, groin, perianal region). The authors present and discuss a case of Pemphigus Vegetans with an unusual clinical presentation lacking involvement of mucous membrane and flexor surfaces in an elderly female patient, associated with the use of enalapril as possible trigger factor. Clinical and histological diagnosis were suggestive of Pemphigus Vegetans of the Hallopeau type.

Epidermodysplasia verruciformis: clinical presentation with varied forms of lesions.

Epidermodysplasia verruciformis is a rare inherited skin disorder spread by HPV, with cases linked to chromosome X. It is characterized by hypo- or hyper-pigmented macular lesions, pityriasis versicolor-like lesions and an early tendency to develop skin malignancies. We present a case of epidermodysplasia verruciformis with a variety of lesions such as multiple plane warts, pityriasis versicolor-like lesions and aggressive squamous cell carcinoma on the face.

Pemphigus vegetans induced by use of enalapril.

Pemphigus Vegetans was first described as a variant of Pemphigus Vulgaris in 1876 by Neumann. In 1889, Hallopeau described a patient with pustules and vegetating plaques, suggesting that it would be a variant of Pemphigus Vegetans of Neumann. Both types of Pemphigus Vegetans are characterized by the development of vegetating plaques especially on skin folds (axillae, groin, perianal region). The authors present and discuss a case of Pemphigus Vegetans with an unusual clinical presentation lacking involvement of mucous membrane and flexor surfaces in an elderly female patient, associated with the use of enalapril as possible trigger factor. Clinical and histological diagnosis were suggestive of Pemphigus Vegetans of the Hallopeau type.

Glucose-dependent insulinotropic peptide receptor expression in the hippocampus and neocortex of mesial temporal lobe epilepsy patients and rats undergoing pilocarpine induced status epilepticus.

The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young male patients with left mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and Fluoro-Jade staining was carried out to investigate the association between the GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx of animals and human samples. The GIPR expression after the Pilo-SE induction increases significantly in the HIP after 1h and 5 days, but not after 12h or 50 days. In the Cx, the GIPR expression increases after 1h, 12h and 5 days, but not 50 days after the Pilo-SE. The expression of GIPR 12h after Pilo-SE was inversely proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR expression patterns were similar to those observed in chronic Pilo-SE animals. No Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in human HIP and Cx. There was a time and region dependent increase of GIPR expression in the HIP and Cx after Pilo-SE that was inversely associated to neuronal degeneration.

Vascular endothelial growth factor overexpression positively modulates the characteristics of periprosthetic tissue of polyurethane-coated silicone breast implant in rats.

BACKGROUND: Capsular contracture is one of the most common complications associated with silicone breast implants. The surface of the implant is one of the factors often associated with the occurrence of capsular contracture. In this study, the authors evaluated the differences in morphologic and molecular characteristics of the capsule formed around polyurethane-coated versus textured-surface silicone implants in rats, mainly the modifications in angiogenesis and the expression of vascular endothelial growth factor (VEGF). METHODS: A pocket was performed on the animal's back, where the silicone implants were introduced. Two groups of animals received a polyurethane-coated silicone implant and the other groups received a textured-surface silicone implant, and the capsules around the prostheses were submitted to histologic and immunohistochemistry analysis, 30 or 90 days after surgery. RESULTS: The capsules around the polyurethane-coated silicone prostheses were significantly thicker than the textured-surface silicone implants. Furthermore, the layer adjacent to the polyurethane-coated silicone implants was more cellular and irregular than the layer around the textured-surface silicone implants. Textured implant periprosthetic capsules presented fewer inflammatory cells and less vascularization than the polyurethane-coated silicone implants. The collagen layer of periprosthetic tissue of textured implants appears to be more continuous and aligned in parallel fashion than polyurethane-coated implants. Immunohistochemical analysis revealed high levels of transforming growth factor-ß and VEGF in the capsules around the polyurethane-coated silicone implants when compared with the textured-surface silicone implants. CONCLUSION: These findings suggest that the intense VEGF expression in capsules around the polyurethane-coated silicone implant is able to improve the tissue vascularization, resulting in a softer capsule compared with the textured-surface silicone implant.

Reconhecimento e quantificação de expressão de imunoistoquímica empregando aprendizado de métricas de distância / Recognition and quantification of immunohistochemistry expression distance metric learning

Este artigo apresenta uma abordagem de segmentação para o reconhecimento e quantificação de expressão de imunoistoquímica (IHC) através do aprendizado de uma métrica de distância. Este método é baseado em duas etapas: treinamento e segmentação. A etapa de treinamento é realizada pela seleção supervisionada de algumas áreas típicas de expressão de IHC na imagem. Nesta etapa o padrão esperado de IHC é estatisticamente caracterizado, onde ocorre o aprendizado da métrica de distância e um espaço característico é modelado. Através desse espaço são obtidos os mapas de similaridade para cada imagem de IHC, com os níveis de intensidade correspondendo ao grau da reação do biomarcador sobre o tecido. A etapa de segmentação é guiada por um parâmetro de escala que controla a quantidade de áreas marcadas com base nos valores de intensidade dos mapas de similaridade. O método é baseado no aprendizado da distância de Mahalanobis para produzir um espaço característico, para posteriormente ser utilizado na distinção entre marcações positivas de expressão de IHC e tecidos normais, bem como quantificar o grau de intensidade da reação. Os resultados obtidos pelo método proposto foram comparados com a classificação linear no espaço de cores HSV (Hue, Saturation and Value) utilizando diferentes categorias de biomarcadores. Os resultados mostram que os limites da fronteira da distribuição dos padrões são mais bem definidos no método proposto, permitindo assim uma melhor discriminação entre tecidos normais e expressão de IHC.

This paper presents a segmentation approach to the recognition and quantification of immunohistochemistry (IHC) expression employing a distance metric learning method. This method is based in a two-step procedure, training and segmentation. The training step is performed by the supervised selection of a few IHC typical stained areas on image. In that step the desired IHC pattern is statistically characterized, where a distance metric is learned and a featured space is created. With this space, similarity maps are obtained by each IHC image with its intensity levels corresponding to degrees of reaction provided by the biomarker over the tissue. The segmentation step is guided by a scale-space parameter that controls the amount of labeled areas based on intensity values of the similarity maps. This method learns a Mahalanobis distance metric to produce a featured space used to distinguish between IHC positive staining and normal tissues, as well as quantifying the reaction intensity degrees. The results obtained by the proposed method were compared to the linear classification on HSV (Hue, Saturation and Value) color space using different biomarkers categories. The comparison results show that the boundary limits of the pattern distributions are better defined in the proposed method, allowing better discrimination between normal tissues and IHC expression.

Inducible nitric oxide synthase in pityriasis lichenoides lesions.

BACKGROUND: Pityriasis lichenoides (PL) is an inflammatory skin disease of unknown etiology. Nitric oxide (NO) has emerged as an important mediator of many physiological functions. The importance of NO-mediated signaling in skin diseases has been reported by several studies. METHODS: A review of clinical records and histopathological slides of 34 patients diagnosed with PL was performed. Three different groups of skin biopsies including PL chronica (24 patients), PL et varioliformis acuta (10 patients) and 15 normal skin samples were subjected to the immunohistochemistry technique for inducible nitric oxide synthase (iNOS) detection. RESULTS: Normal skin group exhibited a few number of iNOS-positive cells in the dermis and rare positive cells in the upper epidermis, unlike abundant epidermal and dermal iNOS expression observed in both PL groups. CONCLUSION: According to our results, we hypothesize that NO produced by iNOS could participate in PL pathogenesis. Abnormal and persistent responses to unknown antigens, probably a pathogen, associated with NO immunoregulatory functions could contribute to the relapsing course observed in PL. NO anti-apoptotic effect on T-cell lymphocytes could play a role on maintenance of reactive T cells, leading to a T-cell lymphoid dyscrasia.

Immunohistochemical study of presence of T cells, B cells, and macrophages in periradicular lesions of primary teeth.

BACKGROUND: The periapical lesion is the result of a local inflammatory reaction caused by bacteria and its products present on the root canal. The interaction between inflammatory cells and bacteria elicit both specific and non-specific immune responses. OBJECTIVE: Due to the lack of studies evaluating the role of the immune system in periapical lesions of primary teeth and considering the potentially systemic effects that these infections can cause in children, especially because of the immaturity of their immune system, we sought to evaluate the presence of T cells, B cells and macrophages on periradicular lesions in primary teeth. STUDY DESIGN: 14 periradicular lesions were analyzed. The immunohistochemistry technique was performed using CD45RO, CD20, CD68 monoclonal antibodies aiming to identify T cells, B cells and macrophages, respectively. Cells were quantified by microscopic analysis of histological sections. RESULTS: Mean percentage of positive cells CD45RO was 11.76; CD20 was 5.25; CD68 was 10.92. Our results showed that T and B cells and macrophages comprise the majority of the inflammatory infiltrate. CONCLUSION: We concluded that both humoral and cell mediated immune reactions take place in periradicular lesions of primary teeth. The immune system plays an important role on the periradicular inflammatory processes in primary teeth.

Connecting TNF-alpha signaling pathways to iNOS expression in a mouse model of Alzheimer's disease: relevance for the behavioral and synaptic deficits induced by amyloid beta protein.

Increased brain deposition of amyloid beta protein (Abeta) and cognitive deficits are classical signals of Alzheimer's disease (AD) that have been highly associated with inflammatory alterations. The present work was designed to determine the correlation between tumor necrosis factor-alpha (TNF-alpha)-related signaling pathways and inducible nitric oxide synthase (iNOS) expression in a mouse model of AD, by means of both in vivo and in vitro approaches. The intracerebroventricular injection of Abeta(1-40) in mice resulted in marked deficits of learning and memory, according to assessment in the water maze paradigm. This cognition impairment seems to be related to synapse dysfunction and glial cell activation. The pharmacological blockage of either TNF-alpha or iNOS reduced the cognitive deficit evoked by Abeta(1-40) in mice. Similar results were obtained in TNF-alpha receptor 1 and iNOS knock-out mice. Abeta(1-40) administration induced an increase in TNF-alpha expression and oxidative alterations in prefrontal cortex and hippocampus. Likewise, Abeta(1-40) led to activation of both JNK (c-Jun-NH2-terminal kinase)/c-Jun and nuclear factor-kappaB, resulting in iNOS upregulation in both brain structures. The anti-TNF-alpha antibody reduced all of the molecular and biochemical alterations promoted by Abeta(1-40). These results provide new insights in mouse models of AD, revealing TNF-alpha and iNOS as central mediators of Abeta action. These pathways might be targeted for AD drug development.

Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

Differential susceptibility following beta-amyloid peptide-(1-40) administration in C57BL/6 and Swiss albino mice: Evidence for a dissociation between cognitive deficits and the glutathione system response.

Considerable evidence supports the role of oxidative stress in the pathogenesis of Alzheimer's disease (AD). Previous studies suggest that the central nervous system (CNS) administration of beta-amyloid peptide, the major constituent of senile plaque in AD, induces oxidative stress in rodents which may contribute to the learning and memory deficits verified in the beta-amyloid model of AD. In the present study, we compared the effects of a single intracerebroventricular (i.c.v.) injection of aggregated beta-amyloid peptide-(1-40) (Abeta(1-40)) (400pmol/mouse) on spatial learning and memory performance, synaptic density and the glutathione (GSH)-dependent antioxidant status in adult male C57BL/6 and Swiss albino mice. Seven days after Abeta(1-40) administration, C57BL/6 and Swiss mice presented similar spatial learning and memory impairments, as evaluated in the water maze task, although these impairments were not found in Abeta(40-1)-treated mice. Moreover, a similar decline of synaptophysin levels was observed in the hippocampus (HC) and prefrontal cortex (PFC) of both Swiss and C57BL/6 mice treated with Abeta(1-40), which suggests synaptic loss. C57BL/6 mice presented lower levels of glutathione-related antioxidant defences (total glutathione (GSH-t) levels, glutathione peroxidase (GPx) and glutathione reductase (GR) activity) in the HC and PFC in comparison to Swiss mice. Despite the reduced basal GSH-dependent antioxidant defences observed in C57BL/6 mice, Abeta(1-40) administration induced significant alterations in the brain antioxidant parameters only in Swiss mice, decreasing GSH-t levels and increasing GPx and GR activity in the HC and PFC 24h after treatment. These results indicate strain differences in the susceptibility to Abeta(1-40)-induced changes in the GSH-dependent antioxidant defences in mice, which should be taken into account in further studies using the Abeta model of AD in mice. In addition, the present findings suggest that the spatial learning and memory deficits induced by beta-amyloid peptides in rodents may not be entirely related to glutathione-dependent antioxidant response.