Immunostaining of stromal CD56 cells in ovarian malignancies.

OBJECTIVES: The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer. METHODS: Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05. RESULTS: We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival. CONCLUSION: Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

Immunostaining of stromal CD56 cells in ovarian malignancies

SUMMARY OBJECTIVES: The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer. METHODS: Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05. RESULTS: We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival. CONCLUSION: Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

Mast cells and M2 macrophages in ovarian cancer.

The objectives of this study were to investigate the immunohistochemical expression of markers of mast cells and M2 macrophages in benign and malignant ovarian neoplasms and to examine the prognostic value of this expression in ovarian cancer. The study was performed with samples from 32 patients, divided into benign (n = 16) and malignant (n = 16) neoplasm groups. Samples obtained by surgical resection were submitted to immunohistochemical analysis. Higher proportions of M2 macrophages (p = .041) and mast cells (p = .0054) were present in malignant than benign ovarian neoplasms. Histological grade 2/3 was related to higher proportions of M2 macrophages compared with grade 1 (p = .0102). Stages II-IV were also related to higher proportions of M2 macrophages (p = .0102). Logistic regression revealed that M2 macrophages predicted malignancy [odds ratio (OR) = 1.017; 95% confidence interval (CI), 1.003-1.037; p = .017], but that mastocytes had greater predictive value for this outcome (OR = 1.127; 95% CI, 1.018-1.105; p = .013). M2 macrophages predicted more advanced histological grades (OR = 1.060; 95% CI, 1.010-1.218; p = .003). The proportions of M2 macrophages and mast cells were greater in malignant than in benign ovarian neoplasms. Larger proportions of cells expressing M2 macrophages were related to more advanced histological grades and disease stages, and thus to worse prognoses for ovarian cancer.Impact StatementWhat is already known on this subject? Concentrations of mast cells and M2 macrophages have been observed in several tumour types, but their significance remains uncertain.What do the results of this study add? The proportions of M2 macrophages and mast cells were greater in malignant than in benign ovarian neoplasms. Larger proportions of cells expressing M2 macrophages were related to higher histological grades and more advanced stages of the disease.What are the implications of these findings for clinical practice and/or further research? Larger proportions of cells expressing M2 macrophages were related to worse prognoses for malignant ovarian neoplasia. The discovery of new prognostic factors in ovarian cancer may be the target of studies on new treatments and immunotherapies for this disease. In addition, it can help guide the oncologist towards more aggressive treatments for patients with worse prognostic factors.

Infiltração de anestésicos locais na ferida cirúrgica: efeito sobre a inflamação e cicatriz fibrosa em ratos / Infiltration of local anesthetics into the surgical wound: effect on inflammation and fibrous scar in rats

■ RESUMO Introdução: O alívio da dor após a cirurgia continua sendo um dos desafios médicos mais significativos, principalmente na cirurgia estética. A infiltração da incisão cirúrgica com anestésicos locais tem sido cada vez mais utilizada para reduzir a dor e o uso de analgésicos. No entanto, pouco se sabe sobre o efeito desta injeção na cicatrização. O objetivo é avaliar a interferência dos anestésicos locais na área de infiltrado inflamatório e cicatriz de fibrose em ratos. Métodos: Duas incisões lineares foram feitas cada uma na região dorsal de 40 ratos Wistar. A incisão esquerda foi infiltrada com doses de 1,8ml de bupivacaína, levobupivacaína, ropivacaína ou solução salina 0,9%. A incisão direita não recebeu infiltração, servindo como grupo controle. Após sete dias, amostras das incisões foram coletadas para avaliação morfométrica histológica. Resultados: Quando comparada com os grupos controle, a área de infiltrado inflamatório encontrada foi maior nos grupos bupivacaína, ropivacaína e levobupivacaína. O grupo bupivacaína apresentou um infiltrado inflamatório maior do que a levobupivacaína e a ropivacaína. A área da cicatriz fibrosa foi maior nos grupos levobupivacaína e ropivacaína. Não houve diferença entre os grupos que receberam anestésico e solução salina. Conclusão: Como não houve diferença entre os grupos de anestésico e soro fisiológico, o volume aplicado ou o trauma podem ter sido a causa das maiores áreas de infiltração e cicatriz associadas à aplicação dos anestésicos locais.

■ ABSTRACT Introduction: Pain relief after surgery remains one of the most significant medical challenges, mainly in aesthetic surgery. The infiltration of the surgical incision with local anesthetics has been increasingly used to reduce pain and other analgesic use. However, little is known about the effect of this injection on healing. The objective is to evaluate the interference of local anesthetics in the area of inflammatory infiltrate and fibrosis scar in rats. Methods: Two linear incisions each were made on the dorsal region of 40 Wistar rats. The left incision was infiltrated with doses of 1.8ml of bupivacaine, levobupivacaine, ropivacaine, or 0,9% saline solution infiltration. The right incision did not receive infiltration, serving as a control group. After seven days, samples of the incisions were collected for histological morphometric evaluation. Results: When compared with the control groups, the area of inflammatory infiltrate was found larger in the bupivacaine, ropivacaine, and levobupivacaine groups. The bupivacaine group presented a larger inflammatory infiltrate than the levobupivacaine and ropivacaine. The fibrous scar area was larger in the levobupivacaine and ropivacaine groups. There was no difference between the groups that received anesthetic and saline solution. Conclusion: As there was no difference between the anesthetics and saline solution groups, the volume applied, or the trauma may have been the cause of the larger areas of infiltrating and scar associated with local anesthetics application.

CHRONIC USE OF PROTON PUMP INHIBITORS AND THE QUANTITY OF G, D, AND ECL CELLS IN THE STOMACH.

BACKGROUND: Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells. AIM: To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection. METHODS: Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands. RESULTS: Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls. CONCLUSION: Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.

Overexpression of HIF-1α and Morphological Alterations in the Tongue of Rats Exposed To Secondhand Smoke.

Smoking is a risk factor for serious health problems and is associated with several changes in the tissues of the oral cavity. The aim of this study was to evaluate the collagen percentage, mast cells density, intensity of immunolabeled cells by anti-HIF-1α in the musculature lingual of rats exposed to secondhand smoke. Twenty-seven female Wistar albino rats were divided into three groups: rats not exposed to tobacco smoke inhalation (Control group) (n=7); rats exposed to smoke inhalation for 30 days (TAB 30) (n=10); and rats exposed to smoke inhalation for 45 days (TAB 45) (n=10). Subsequently, the animals were submitted to euthanasia and removal of the tongue for histological and immunohistochemistry processing and analysis. In the groups TAB 30 and TAB 45 there were a lower percentage of collagen, a higher density of mast cells and a greater intensity of anti-HIF-1α immunolabeled cells compared to Control group. There was also a positive and significant correlation between the percentage of collagen and mast cell density. There was not significative difference between TAB 30 e TAB 45 in any of the parameters evaluated. Therefore, the exposure of rats to secondhand smoke for 45 days causes decrease in perimysial collagen fibers, increase in the number of mast cells and increase in the immunolabeling for HIF-1α in lingual muscle cells. The present study was the first to evaluate the percentage of collagen, mast cell density and immunostaining for HIF-1α in rat tongues exposed to tobacco smoke.

Overexpression of hif-1α and morphological alterations in the tongue of rats exposed to secondhand smoke

Abstract Smoking is a risk factor for serious health problems and is associated with several changes in the tissues of the oral cavity. The aim of this study was to evaluate the collagen percentage, mast cells density, intensity of immunolabeled cells by anti-HIF-1α in the musculature lingual of rats exposed to secondhand smoke. Twenty-seven female Wistar albino rats were divided into three groups: rats not exposed to tobacco smoke inhalation (Control group) (n=7); rats exposed to smoke inhalation for 30 days (TAB 30) (n=10); and rats exposed to smoke inhalation for 45 days (TAB 45) (n=10). Subsequently, the animals were submitted to euthanasia and removal of the tongue for histological and immunohistochemistry processing and analysis. In the groups TAB 30 and TAB 45 there were a lower percentage of collagen, a higher density of mast cells and a greater intensity of anti-HIF-1α immunolabeled cells compared to Control group. There was also a positive and significant correlation between the percentage of collagen and mast cell density. There was not significative difference between TAB 30 e TAB 45 in any of the parameters evaluated. Therefore, the exposure of rats to secondhand smoke for 45 days causes decrease in perimysial collagen fibers, increase in the number of mast cells and increase in the immunolabeling for HIF-1α in lingual muscle cells. The present study was the first to evaluate the percentage of collagen, mast cell density and immunostaining for HIF-1α in rat tongues exposed to tobacco smoke.

Resumo O tabagismo é um fator de risco para sérios problemas de saúde e está associado a diversas alterações nos tecidos da cavidade oral. O objetivo deste estudo foi avaliar a porcentagem de colágeno, densidade de mastócitos e intensidade de células imunomarcadas por anti-HIF-1α na musculatura lingual de ratos expostos passivamente à fumaça principal do cigarro. Vinte e sete ratos Wistar albinos fêmeas foram divididos em três grupos: ratos não expostos à inalação da fumaça do tabaco (grupo controle) (n=7); ratos expostos à inalação da fumaça por 30 dias (TAB 30) (n=10); e ratos expostos à inalação da fumaça por 45 dias (TAB 45) (n=10). Posteriormente, os animais foram submetidos à eutanásia e remoção da língua para processamento e análise histológica e imuno-histoquímica. Nos grupos TAB 30 e TAB 45, houve diminuição do percentual de colágeno, maior densidade de mastócitos e maior intensidade de células imunomarcadas por anti-HIF-1α em comparação ao grupo controle. Houve também correlação positiva e significativa entre a porcentagem de colágeno e a densidade de mastócitos. Não houve diferença significativa entre TAB 30 e TAB 45 em nenhum dos parâmetros avaliados. Portanto, a exposição passiva de ratos à fumaça principal do cigarro por 45 dias provoca diminuição das fibras de colágeno perimisial, aumento do número de mastócitos e aumento da imunomarcação para o HIF-1α em células musculares linguais. O presente estudo foi o primeiro a avaliar a porcentagem de colágeno, densidade de mastócitos e imunomarcação para o HIF-1α em línguas de ratos expostos à fumaça do tabaco.

Histoplasmosis in HIV-Infected Patients: Epidemiological, Clinical and Necropsy Data from a Brazilian Teaching Hospital.

Histoplasmosis occurs in 5-10% of HIV-infected patients in endemic areas and evolves to severe and disseminated infection with mortality rates over 50% in some regions. This report presents epidemiological, clinical and outcome data from HIV-infected patients with histoplasmosis confirmed by culture and/or at necropsy who were admitted to a Brazilian teaching hospital. Data from 65 patients were obtained from their respective medical and necropsy records. From 2005 to 2018, 36 HIV-infected patients were diagnosed with histoplasmosis confirmed by culture. At admission, most of these patients presented disseminated fungal infection, whereas 15 (41.7%) were simultaneously diagnosed with both HIV infection and histoplasmosis. Fever, weight loss, hepatosplenomegaly, respiratory and digestive symptoms were present in 86.2%, 50%, 44.4% and 41.7% of the patients, respectively. At admission, 24 patients had low CD4 T-cell count and high viral load values. Among the 30 patients who received antifungals, 16 (53.3%) were cured, 13 (43.3%) died, and one was lost to follow-up. Six patients died prior to therapy. From 1990 to 2018, 63 necropsies of patients with Histoplasma capsulatum infection were performed. Of these patients, 29 (46.0%) were HIV-infected individuals, including 21 (72.4%) who presented disseminated histoplasmosis and 21 (72.4%) who were diagnosed with histoplasmosis at necropsy. The epidemiological, clinical and outcome profiles presented herein are similar to those described elsewhere and reinforce the difficulties that are still present in limited-resource settings where advanced immunodeficiency, combined with severe fungal infection and late patient admissions, is related to poor outcomes.

Lymphocytes in Peritumoral Stroma: Evaluation in Epithelial Ovarian Neoplasms.

Background: Ovarian cancer is a heterogeneous disease, where chronic inflammation is one of the central mechanisms of its pathogenesis. The objectives of the study were to evaluate the expression of CD3, CD4, CD8 and CD20 in the peritumoral stroma of benign and malignant ovarian epithelial neoplasms and to relate them to prognostic factors in ovarian cancer.Methods: We evaluated 77 patients (40 benign epithelial ovarian neoplasms and 37 malignant epithelial ovarian neoplasms). Immunohistochemistry study for cytokines (CD3, CD4, CD8 and CD20) was performed. The evaluation of prognostic factors was performed using the Fisher's exact test. The significance level was less than 0.05.Results: A higher CD3 expression was found in the stroma of ovarian malignancies compared benign neoplasms, and greater expression of CD4 cells in the stroma of benign neoplasms compared to ovarian cancer. There was a greater expression of CD8 cells in the stromal ovarian malignancies with molecular type II compared to type I. In the evaluation of lymph node metastases, the absence of immuno-labelling of CD20 cells was associated with the absence of lymph node metastases.Conclusion: The immune system plays a multifaceted role and can promote or inhibit tumor growth in different contexts.

Chronic use of proton pump inhibitors and the quantity of g, d, and ecl cells in the stomach / Uso crônico de inibidores de bomba de prótons e a quantidade de células g, d e ecl no estômago

ABSTRACT Background: Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells. Aim: To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection. Methods: Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands. Results: Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls. Conclusion: Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.

RESUMO Racional: A inibição ácida pelo uso crônico de inibidores de bomba de prótons e o possível aumento da gastrina podem ser seguidos de alterações na regulação da produção do ácido clorídrico. Ainda não está definido se o uso crônico altera a quantidade de células G, D e ECL no estômago ou a razão células G/D. Objetivo: Avaliar o número de células G - produtoras de gastrina -, células D - produtoras de somatostatina - e células ECL - produtoras de histamina -, em pacientes com uso crônico de inibidores de bomba de prótons, com ou sem infecção pelo Helicobacter pylori. Método: Trata-se de estudo retrospectivo avaliando 105 pacientes, 81 usadores crônicos de inibidores de bomba de prótons e 24 controles, através de biópsias com contagem das células G, D e ECL por estudo imunoistoquímico, de forma quantitativa onde havia maior número de células positivas por campo microscópico de grande aumento e em 10 glândulas. Resultados: Não houve diferença estatística comparando-se o número de células G, D e ECL. A razão entre as células G e D foi maior nos pacientes usadores crônicos de inibidores de bomba de prótons. Conclusão: O uso crônico de inibidores de prótons parece não interferir na contagem das células G, D e ECL, porém, interfere na razão entre as células G e D.

Lingual salivary gland hypertrophy and decreased acinar density in chagasic patients without megaesophagus.

Although the salivary glands present several functions, there are few studies evaluating these glands in Chagas disease (CD). This study aimed to compare the percentage of collagen, the presence of inflammation, the density of chimase and tryptase mast cells, the area and density of lingual salivary gland acini in autopsied individuals with and without (CD). We analyzed 400 autopsy reports performed in a tertiary public hospital from 1999 to 2015 and selected all the cases in which tongue fragments were collected (27 cases), 12 with chronic CD without megaesophagus (CH) and 15 without CD (non-chagasic - NC). The histological sections of the tongue were stained by Picrosirius red for collagen evaluation and Hematoxylin-eosin for morphometric evaluation of salivary gland acini and inflammation. Anti-chimase and anti-tryptase antibodies were used for the immunohistochemical evaluation of mast cells. The chagasic patients presented higher volume and lower density of salivary glands acini. There was no difference in the collagen percentage, inflammation and density of mast cell chymase and tryptase between the groups. Although we did not observe a significant difference between the groups regarding the collagen percentage, inflammatory process and mast cell density, our results suggest that even without megaesophagus, chagasic patients present hypertrophy of the lingual salivary glands and lower acinar density probably due to mechanisms independent of the esophagus-glandular stimulus.

Hemophagocytic Lymphohistiocytosis in Autopsied Adults: Clinical, Laboratory and Immunohistochemical Evaluation for CD68 and CD57. Case Report and Literature Review / Linfohistiocitose Hemofagocítica em Adultos Autopsiados: Avaliação Clínica, Laboratorial e Imunohistoquímica para CD68 e CD57. Relato de Caso e Revisão de Literatura

Hemophagocytic lymphohistiocytosis (HLH) is a rare, usually fatal and underdiagnosed autoimmune-activated disease. The present study aimed to perform a macroscopic, histopathological and immunohistochemical evaluation for CD68 and CD57 in organs of autopsied adults with HLH. A total of 604 autopsy reports were analyzed, and all the patients that filled the diagnostic criteria for HLH (n = 2) were selected. These patients were 18 and 37 years old. Were evaluated both clinical and autopsy reports and performed histopathological and immunohistochemical analysis of the liver and spleen. Both patients filled the diagnostic criteria for HLH, as well as presented common signs and symptoms of this disease, such as chills, abdominal pain, diaphoresis, and jaundice. Hemophagocytosis was observed in the spleen, bone marrow, and lymph nodes of the two patients at autopsy. Immunostaining in the liver and spleen of both patients was mainly severe for CD68, and predominantly mild for CD57, indicating a decrease in NKC numbers and an increase in the number of macrophages, respectively. This was the first study to evaluate CD57 and CD68 in autopsies of adults with HLH. Thus, more studies are required, not only to better elucidate the pathogenetic mechanisms involved in the secondary HLH, but also to disseminate the results in the clinical environment, contributing to the early diagnosis and treatment with consequent reduction of mortality rate. (AU)

A Linfohistiocitose Hemofagocítica (HLH) é uma doença autoimune rara, geralmente fatal e subdiagnosticada. Este estudo tem como objetivo realizar avaliação macroscópica, histopatológica e imunohistoquímica para CD68 e CD57 em órgãos de pacientes adultos com HLH submetidos a autópsia. Um total de 604 laudos de autópsias foram analisados e todos os pacientes que preencheram os critérios diagnósticos para HLH (n = 2) foram selecionados. Esses pacientes tinham 18 e 37 anos de idade. Foram analisados tanto os prontuários quanto os laudos de autópsia, bem como foram realizadas análises histopatológicas e imunohistoquímicas do fígado e baço dos pacientes. Ambos preencheram os critérios diagnósticos para HLH e apresentarem sinais e sintomas comuns da doença, como calafrios, dor abdominal, sudorese e icterícia. A hemofagocitose foi observada no baço, medula óssea e linfonodos dos dois pacientes na autópsia. A imunohistoquímica do fígado e do baço de ambos os pacientes demonstrou imunomarcação acentuada para CD68 e predominantemente discreta para CD57, que indicam diminuição do número de NKC e aumento do número de macrófagos, respectivamente. Este foi o primeiro estudo a avaliar o CD57 e CD68 em autópsias de adultos com HLH. Assim, mais estudos são necessários, não apenas para melhor elucidar os mecanismos patogenéticos envolvidos na HLH secundária, mas também para disseminar os resultados no ambiente clínico, contribuindo para o diagnóstico e tratamento precoces com consequente redução da taxa de mortalidade. (AU)

Increased serum gastrin in patients with different clinical forms of Chagas disease coinfected with Helicobacter pylori.

Trypanosoma cruzi and Helicobacter pylori (HP) are pathogens that cause chronic diseases and have been associated with hypergastrinemia. The aim of this study was to evaluate the fasting gastrin levels in patients with different clinical forms of Chagas disease (CD), coinfected or not by HP. The enrolled individuals were outpatients attending at the university hospital. HP infection was assessed by serology and 13 C-urea breath test. Fasting serum gastrin concentration was measured by chemiluminescence assay. Gastric endoscopic and histological features were also evaluated. Associations between CD and serum gastrin level were evaluated in a logistical model, adjusting for age, gender and HP status. A total of 113 patients were evaluated (45 with Chagas disease and 68 controls). In the multivariate analysis, increasing serum gastrin levels (OR= 1.02; 95% CI= 1.01-1.12), increasing age (OR= 1.05; 95% CI= 1.02 - 1.09) and HP-positive status (OR = 2.88; 95% CI = 1.10 - 7.51) remained independently associated with CD. The serum gastrin levels were significantly higher in the group of patients with the cardiodigestive form ( P = 0.03) as well as with digestive form ( P = <0.001) of Chagas disease than in the controls. In conclusion, patients with cardiodigestive and digestive clinical forms of CD have increased basal serum gastrin levels in comparison with controls. Moreover, we also demonstrated that H. pylori coinfection contributes to the hypergastrinemia shown in CD.

Melatonin treatment in fetal and neonatal diseases.

This literature review aims to address the main scientific findings on oxidative stress activity in different gestational disorders, as well as the function and application of melatonin in the treatment of fetal and neonatal changes. Oxidative stress has been associated with the etiopathogenesis of recurrent miscarriages, preeclampsia, intrauterine growth restriction, and stillbirth. Both, the exacerbated consumption of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and the increased synthesis of reactive oxygen species, such as superoxide, peroxynitrite, and hydrogen peroxide, induce phospholipid peroxidation and endothelial dysfunction, impaired invasion and death of trophoblast cells, impaired decidualization, and remodeling of maternal spiral arteries. It has been postulated that melatonin induces specific biochemical responses that regulate cell proliferation in fetuses, and that its antioxidant action promotes bioavailability of nitric oxide and, thus, placental perfusion and also fetal nutrition and oxygenation. Therefore, the therapeutic action of melatonin has been the subject of major studies that aim to minimize or prevent different injuries affecting this pediatric age group, such as intrauterine growth restriction, encephalopathy, chronic lung diseases, retinopathy of prematurity Conclusion: the results antioxidant and indicate that melatonin is an important therapy for the clinical treatment of these diseases.

Avaliação histológica do músculo grande dorsal submetido à expansão tecidual pós-infiltração com toxina botulínica: estudo experimental em ratas / Histological evaluation of latissimus dorsi muscle subjected to tissue expansion after infiltration with botulinum toxin: an experimental study in rats

Os autores descrevem as alterações histológicas no músculo grande dorsal submetido à expansão após relaxamento com toxina botulínica e as possíveis correlações dos achados com os benefícios práticos como, por exemplo, aumento da complacência muscular e melhor acomodação da prótese. Foi empregado o modelo experimental, com dez ratas com peso médio de 300 g, mesma faixa etária, da cepa Wistar (Rattus norvegicus) e o músculo grande dorsal. Biópsias musculares foram feitas antes e após as expansões, no músculo normal, no grupo controle (apenas com expansores) e no grupo com expansores e toxina botulínica. Expansores de 3 centímetros cúbicos eram posicionados abaixo do músculo e expandidos com 0,3 mililitros de soro fisiológico semanalmente, por 10 semanas. Os cortes histológicos foram corados segundo as técnicas de Hematoxilina-eosina, para avaliação geral, e tricrômio de Masson para avaliação do tecido conjuntivo. As fibras musculares submetidas à expansão sob a ação da toxina botulínica apresentaram focos de fibrose e proliferação de vasos sanguíneos menos intensos que no grupo sem toxina botulínica e a diminuição do número de fibras musculares e a atrofia eram menores que no grupo que não utilizou a toxina. Os achados nos permitem presumir que a expansão muscular associada ao relaxamento com toxina botulínica preserva as características da musculatura esquelética, oferecendo melhor acomodação e proteção da prótese e facilitando a dinâmica da expansão, além de diminuir a dor.

The authors describe histological changes in the latissimus dorsi muscle submitted to expansion after relaxation with botulinum toxin. The possible practical benefits include increased muscle compliance and better accommodation of a prosthesis. The experimental model involved 10 Wistar rats (Rattus norvegicus) of the same age, with average weight of 300 g. Muscle biopsies before and after expansion were performed in normal muscle, in a control group (with expanders alone), and in a group with expanders and botulinum toxin. Expanders measuring 3 cm3 were positioned below the muscle and expanded with 0.3 ml of saline weekly, for 10 weeks. Histological sections were stained using hematoxylin-eosin for general evaluation and Masson's trichrome for evaluation of connective tissue. The muscle fibers submitted to expansion under the action of botulinum toxin showed less fibrosis and less intense proliferation of blood vessels than in the group without botulinum toxin, and the atrophy and reduction in the number of muscle fibers were less prominent than in the group that did not receive botulinum toxin. The findings suggest that muscle expansion associated with botulinum toxin relaxation preserves skeletal muscle characteristics by providing better accommodation and protection for a prosthesis and facilitating expansion dynamics; this method may also reduce pain.

Role of Alpha-Smooth Muscle Actin and Fibroblast Activation Protein Alpha in Ovarian Neoplasms.

BACKGROUND/AIMS: Studies show that tumor growth is not just determined by the presence of malignant cells, since interactions between cancer cells and stromal microenvironment have important impacts on the cancer growth and progression. Cancer-associated fibroblasts play a prominent role in this process. The aims of the study were to investigate 2 cancer-associated fibroblasts markers, alpha-smooth muscle actin (α-SMA), and fibroblast activation protein alpha (FAP) in the stromal microenvironment of benign and malignant ovarian epithelial neoplasms, and to relate their tissue expression with prognostic factors in ovarian cancer. METHODS: α-SMA and FAP were evaluated by immunohistochemistry in malignant (n = 28) and benign (n = 28) ovarian neoplasms. Fisher's exact test was used with a significance level lower than 0.05. RESULTS: FAP immunostaining was stronger in ovarian cancer when compared to benign neoplasms (p = 0.0366). There was no significant difference in relation to α-SMA expression between malignant and benign ovarian neoplasms as well as prognostic factors. In ovarian cancer, FAP stainings 2/3 was significantly related to histological grades 2 and 3 (p = 0.0183). CONCLUSION: FAP immunostaining is more intense in malignant neoplasms than in benign ovarian neoplasms, as well as in moderately differentiated and undifferentiated ovarian carcinomas compared to well-differentiated neoplasms, thus indicating that it can be used as a marker of worse prognosis.

Angiogenic and antiangiogenic factors in preeclampsia.

BACKGROUND: Pre-eclampsia is a multifactorial hypertensive disorder that is triggered by placental insufficiency and that accounts for up to 15% of maternal deaths. In normal pregnancies, this process depends on the balance between the expression of angiogenic factors and antiangiogenic factors, which are responsible for remodeling the spiral arteries, as well as for neoangiogenesis and fetal development. PURPOSE: The aim of this review is to discuss the main scientific findings regarding the role of angiogenic and antiangiogenic factors in the etiopathogenesis of preeclampsia. METHODS: An extensive research was conducted in the Pubmed database in search of scientific manuscripts discussing potential associations between angiogenic and antiangiogenic factors and preeclampsia. Ninety-one papers were included in this review. RESULTS: There is an increased expression of soluble fms-like tyrosine kinase receptor and soluble endoglin in pre-eclampsia, as well as reduced placental expression of vascular endothelial growth factor and placental growth factor. Systemic hypertension, proteinuria and kidney injury - such as enlargement and glomerular fibrin deposit, capillary occlusion due to edema, and hypertrophy of endocapillary cells - are some of these changes. The complex etiopathogenesis of preeclampsia instigates research of different biomarkers that allow for the early diagnosis of this entity, such as vascular endothelial growth factor, placental growth factor, soluble fms-like tyrosine kinase receptor, soluble endoglin, placental glycoprotein pregnancy-associated plasma protein-A and protein 13. CONCLUSION: Even though it is possible to establish an efficient and effective diagnostic tool, three key principles must be observed in the management of preeclampsia: prevention, early screening and treatment.

Intrauterine infection, immune system and premature birth.

Preterm birth accounts for nearly one million deaths among children under five years of age, and although its etiopathogenesis is not fully elucidated, ascending intrauterine infection and fetal inflammatory response seem to be the main triggers. The intense inflammatory response mediated by IL-1ß, TNF-α, PAF, IFN-γ and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage and rupture, increased uterine contractions and biochemical and structural changes in the cervix. Furthermore, preterm neonates have deficient innate and adaptive immune responses characterized by reduced levels of IgG, opsonization and phagocytosis, as well as increased activation of Th1 cells in relation to Th2 cells. Therefore, this triad is favors the occurrence of neonatal complications, such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Due to serious maternal and child health complications of intrauterine infection, several studies have tried to identify biomarkers for the early diagnosis of this entity. This literature review aims to discuss the main scientific findings regarding the association between ascending intrauterine infection, immune system and preterm birth.