Nanoparticles and phototherapy combination as therapeutic alternative in prostate cancer: A scoping review.

Prostate cancer (CaP) is one of the most common types of cancers worldwide. Despite the existing surgical techniques, prostatectomy patients may experience tumor recurrence. In addition, castration-resistant cancers pose a challenge, especially given their lack of response to standard care. Thus, the development of more efficient therapies has become a field of great interest, and photothermal therapy (PTT) and photodynamic therapy (PDT) are promising alternatives, given their high capacity to cause cell injury and consequent tumor ablation. Phototherapy, along with chemotherapy, has also been shown to be more effective than pharmacotherapy alone. Free molecules used as photosensitizers are rapidly cleared from the body, do not accumulate in the tumor, and are primarily hydrophobic and require toxic solvents. Thus, the use of nanoparticles can be an effective strategy, given their ability to carry or bind to different molecules, protecting them from degradation and allowing their association with other surface ligands, which favors permeation and retention at the tumor site. Despite this, there is still a gap in the literature regarding the use of phototherapy in association with nanotechnology for the treatment of CaP. In this scoping review, it was found that most of the particles studied could act synergistically through PDT and PTT. In addition, fluorescent quenchers can act as diagnostic and therapeutic tools. However, future clinical studies should be performed to confirm the benefits and safety of the combination of nanoparticles and phototherapy for CaP.

Effectiveness of the polyphenols-rich Sedum dendroideum infusion on gastric ulcer healing in rats: Roles of protective endogenous factors and antioxidant and anti-inflammatory mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms.

Natural products have been recognized as important bioactive compounds on the basis of their wide biological properties. Here we investigated the antitumor effect and molecular mechanisms of the diterpene Fruticuline A (fruti) from Salvia lachnostachys, in human cancer cell lineages and Solid Ehrlich Carcinoma in mice. Fruti reduced MCF-7 and HepG2 proliferation by the reduction of Cyclin D1 levels and decreased NF-κB gene levels in both cell types. Furthermore, fruti also induced apoptosis in HepG2 cells, reduced Bcl-2 gene expression and induced necroptosis by increasing Ripk in MCF-7 cells. In mice, fruti prevented tumor development and reduced Cyclin D1, Bcl-2 and Rela gene levels, and reduced the p-NF-κB/NF-κB ratio in tumor tissue. Furthermore, fruti induced necrosis and apoptosis, increased N-acetyl-ß-D-glucosaminidase and TNF-α levels and reduced IL-10 and Vegf levels in tumor tissue. Collectively, fruti exerts antitumor effects through the inhibition of the NF-κB pathway, reducing Cyclin D1 and Bcl-2 levels. In vitro the apoptosis and necroptosis pathways are involved in the cellular death, whereas in vivo, cells undergo necrosis by increased tumor inflammation and reduction of angiogenesis. Thus, fruticuline A acts in tumor cells by multiple mechanisms and represents a promising molecule for drug development in cancer treatment.

Maternal and fetal outcome of pregnancy in Swiss mice infected with Plasmodium berghei ANKAGFP.

Malaria in pregnant women is associated with risk of maternal and perinatal morbidity and mortality, and there are few antimalarial drugs considered safe to treat them, so it is necessary to develop safer antimalarial medicines. The goal of this study was to develop an animal model for human malaria during pregnancy by characterizing the maternal and fetal outcomes in malaria infected Swiss mice. For that, in the present study, we evaluated the outcome of pregnancy in Swiss mice infected with Plasmodium berghei ANKAGFP. We observed a reduction of fetal body weight and signs of skeletal ossification retardation in the offspring of mice infected on GD 12. The group of mice infected with malaria presented premature deliveries and histopathology changes consistent with placental malaria. Our study suggests that Swiss Webster mice infected with P. berghei ANKAGFP on GD 12 might be a valuable model to investigate the safety and the efficacy of new antimalarial drugs indicated to pregnant women.

Salvia lachnostachys Benth has antitumor and chemopreventive effects against solid Ehrlich carcinoma.

Salvia lachnostachys is an herbaceous plant with anti-inflammatory, analgesic and cytotoxic properties. This study investigated the antitumor effect of an ethanolic extract of Salvia lachnostachys leaves (EES) in a solid Ehrlich carcinoma model. Ehrlich cells were inoculated subcutaneously in the right pelvic member (2 × 106 cells) in female Swiss mice. The animals were treated with vehicle (10 mL kg-1, p.o.), EES (30 and 100 mg kg-1, p.o.), or methotrexate (2.5 mg kg-1, i.p.) for 21 days (early treatment) or 14 days (late treatment) after tumor inoculation, or 10 days before tumor inoculation and continued for 21 days after tumor inoculation (chemopreventive treatment). The acute toxicity test was performed according OECD guidelines Late treatment with EES had no antitumor effect. Early treatment with 100 mg kg-1 EES prevented tumor development, increased tumor necrosis factor-α (TNF-α) levels and decreased tumor superoxide dismutase (SOD) activity, interleukin-10 (IL-10) levels and Cyclin D1 expression, and tumor cell necrosis was observed. Chemopreventive treatment with EES for 10 and 31 days prevented tumor development in the same manner. EES treatment for 31 days decreased hepatic and tumor SOD activity, tumor IL-10 levels and Cyclin D1 expression, and increased tumor reduced glutathione, N-acetylglucosaminidase, reactive oxygen species, lipid peroxidation, TNF-α levels and Nrf2 expression. No toxicity was observed in the acute toxicity assay. In conclusion, EES had an antitumor effect by inhibiting Cyclin D1 expression and increasing inflammation with early and chemopreventive treatment. Modulation of the antioxidant system also contribute for the antitumor effects of EES.

Antineoplastic effect of pectic polysaccharides from green sweet pepper (Capsicum annuum) on mammary tumor cells in vivo and in vitro.

The present study investigated the antineoplastic effects of pectic polysaccharides that were extracted from green sweet pepper (Capsicum annuum [CAP]) in the Ehrlich carcinoma in mice and in human mammary tumor lineages. After the subcutaneous inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice received 50, 100, or 150 mg/kg CAP or vehicle orally once daily or methotrexate (2.5 mg/kg, i.p., every 5 days) for 21 days. CAP dose-dependently reduced Ehrlich tumor growth. It also reduced the viability of MCF-7, MDA-MB-231, and MDA-MB-436 human mammary cell lineages. Treatment with CAP reduced the gene expression of vascular endothelial growth factor in vivo and in vitro, reduced vessel areas of the tumors, and induced necrosis in Ehrlich solid tumors. CAP treatment significantly increased Interleukin-6 in tumors. The antineoplastic effect of CAP appears to depend on the regulation of inflammation and angiogenesis. Further studies are encouraged to better understand the CAP potential for the treatment of breast tumors.

Effect of simvastatin on sensorial, motor, and morphological parameters in sciatic nerve crush induced-neuropathic pain in rats.

The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.

Ameloblastoma: Relato de Caso e revisão da literatura com enfoque na nova classificação da organização mundial da saúde de Tumores Odontogênicos / Ameloblastoma: Case Report and literature review with focus in the new World Health Organization classification of Odontogenic Tumors

Ameloblastoma é uma neoplasia epitelial odontogênica localmente agressiva, com crescimento lento e, na maioria dos casos, benigna. Apresenta alto índice de recorrência se não for corretamente removido (1). Ameloblastoma é o segundo tumor odontogênico mais comum, com distribuição semelhante entre os gêneros. Ocorre principalmente na terceira década de vida e cerca de 91,7% ocorre na mandíbula e 8,3% na maxila (1, 3). A incidência anual da neoplasia varia entre 1,5 a 2,41 casos por milhão (4, 5). Na classificação da OMS de 2005 sobre tumores odontogênicos, o ameloblastoma era dividido em: sólido/ multicístico, extraósseo/ periférico, desmoplásico e unicístico. Na mais recente classificação de 2017 o ameloblastoma é dividido em três tipos: ameloblastoma; ameloblastoma unicístico e ameloblastoma extraósseo/ periférico. Verificou-se nos estudos subsequentes que a classificação anterior não demonstrava significado biológico relevante, sendo alguns reclassificados apenas como sub-tipos histológicos

Ameloblastoma is a slow growing and locally agressive odontogenic neoplasm, most of them are benign. It has a high rate of recurrence if not adequate ressected (1). Ameloblastoma is the second most commun odontogenic tumour. It exhibits no gender predilection. Most cases are diagnosed between 20 and 40 years of age. 91,7% occurs in mandible and 8,3% in maxillary region (1,3). The annual incidence rate ranges from 1,5 to 2,41 per million population (4,5). In the former World Health Organizantion Classification of Odontogenic tumors, published in 2005, ameloblastoma was classified as a benign tumour divided in: Ameloblastoma solid/ multicystic type; Ameloblastoma extraosseous/peripheral type; Ameloblastoma desmoplastic type and Ameloblastoma unicystic type. In the last classification, just published in 2017, it is divided in three types only: Ameloblastoma; Ameloblastoma unicystic type and Ameloblastoma extraosseous/peripheral type. It was concluded in the latter studies that the previous classification did not have a relevant biological significance, some of them being reclassified as histological subtypes

Inulin-type fructan and infusion of Artemisia vulgaris protect the liver against carbon tetrachloride-induced liver injury.

BACKGROUND: Infusions of aerial parts of Artemisia vulgaris L. (Asteraceae) are used in herbal medicine to treat several disorders, including hepatosis. PURPOSE: Evaluation of in vivo hepatoprotective effects of A. vulgaris infusion (VI) and inulin (VPI; i.e., the major polysaccharide of VI). STUDY DESIGN: The hepatoprotective effect of A. vulgaris extracts on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism involved in this protection were investigated in mice. METHODS: A. vulgaris infusion (VI) was prepared according to folk medicine using the aerial parts of the plant. Carbohydrate, protein, and total phenolic content was determined in VI, and its phenolic profile was determined by high-performance liquid chromatography (HPLC). Male Swiss mice were orally pretreated for 7 days with VI or VPI (once per day). On days 6 and 7 of treatment, the mice were intraperitoneally challenged with CCl4. Liver and blood were collected and markers of hepatic damage in plasma and oxidative stress in the liver were analyzed. Hepatic histology and inflammatory parameters were also studied in the liver. The scavenging activity of VI and VPI were evaluated in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: VI contained 40% carbohydrates, 2.9% proteins and 9.8% phenolic compounds. The HPLC fingerprint analysis of VI revealed chlorogenic, caffeic and dicaffeoylquinic acids as major low-molar-mass constituents. Oral pretreatment with VI and VPI significantly attenuated CCl4-induced liver damage, reduced the activity of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in plasma, and prevented reactive oxygen species accumulation and lipid peroxidation in the liver. Comparisons with the CCl4-treated group showed that VI and VPI completely prevented necrosis, increased the levels of reduced glutathione (GSH), and reduced tumor necrosis factor alpha (TNF-α) level in the liver. VI and VPI also exhibited high radical scavenging activity in vitro. CONCLUSION: VI and VPI had remarkable hepatoprotective effects in vivo, which were likely attributable to antioxidant and immunomodulatory properties. The present findings support the traditional use of A. vulgaris infusion for the treatment of hepatic disorders.

The detection of Bence Jones protein in urine by the heat test helps in diagnosis of multiple myeloma? / A detecção de proteína Bence Jones na urina pelo teste de calor auxilia no diagnóstico de mieloma múltiplo?

ABSTRACT Introduction: Multiple myeloma (MM) is a hematologic malignancy caused by the intense indiscriminate proliferation of plasma cells in the bone marrow. In view of clinical suspicion of MM, clinic laboratory tests and imaging tests should be used, among others. Objectives: Evaluate the laboratory test for protein detection heat method Bence Jones (BJ) used to complementary diagnosis pathology and to characterize the epidemiological profile of patients diagnosed with MM. Material and methods: A retrospective study was conducted from January 2010 to July 2015 of the patients treated at Hospital de Clínicas of Universidade Federal do Paraná (HC/UFPR) in Curitiba, Paraná, Brazil. Results: In the patients analyzed, the average age at diagnosis of MM was 65.6 years, with a minimum percentage of difference between genders [males 52.6% (n = 10) and females 47.4% (n = 9)], predominantly in the white race [84.2% (n = 16)]. Among the patients analyzed, 85.2% (n = 104) had negative BJ exam and 14.8 (n = 18), positive exam; 84.4% (n = 103) had no diagnosis of MM, and 15.6% (n = 19) were diagnosed with the disease. Conclusion: The evaluation results of BJ protein detection by the heat method showed sensitivity of 47.4%, specificity of 91.3%, with positive and negative predictive values of 50% and 90.4%, respectively.

RESUMO Introdução: O mieloma múltiplo (MM) é uma neoplasia maligna hematológica causada pela intensa proliferação indiscriminada de plasmócitos na medula óssea. Diante da suspeita clínica de MM devem ser realizados exames laboratoriais e exames de imagem, entre outros. Objetivos: Avaliar o teste laboratorial de calor para detecção de proteína Bence Jones (BJ), utilizado como diagnóstico complementar da patologia, e caracterizar o perfil epidemiológico dos pacientes diagnosticados com MM. Material e métodos: Foi realizado um estudo retrospectivo de janeiro de 2010 a julho de 2015 dos pacientes atendidos no laboratório do Hospital de Clínicas da Universidade Federal do Paraná (UFPR), Curitiba, Paraná, Brasil. Resultados: Dos pacientes avaliados, a média de idade no momento do diagnóstico de MM foi de 65,6 anos, com um percentual de diferença mínima entre os gêneros masculino [52,6% (n = 10)] e feminino [47,4% (n = 9)] e predomínio na raça branca [84,2% (n = 16)]. Entre os pacientes analisados, 85,2% (n = 104) apresentaram exame de BJ negativo e 14,8 (n = 18), positivo; 84,4% (n = 103) não apresentaram diagnóstico de MM e 15,6% (n = 19) foram diagnosticados com a patologia. Conclusão: Os resultados da avaliação do método de calor de detecção de proteína BJ mostraram sensibilidade de 47,4% e especificidade de 91,3%, com valores preditivos positivo e negativo de 50% e 90,4%, respectivamente.

Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats.

Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls. Treatment with 60mg/kg SFP reduced blood monocytes and neutrophils, reduced the tumor activity of N-acetylglucosaminidase, myeloperoxidase, and nitric oxide, increased blood lymphocytes, and increased the levels of tumor necrosis factor α (TNF-α) in tumor tissue. Treatment with SFP also induced the expression of the cell necroptosis-related genes Rip1 and Rip3. The antineoplastic effect of SFP appears to be attributable to its action on the immune system by controlling the tumor microenvironment and stimulating TNF-α production, which may trigger the necroptosis pathway.

Hydroethanolic extract of Baccharis trimera ameliorates alcoholic fatty liver disease in mice.

Ethanol abuse is a serious public health problem that is associated with several stages of alcoholic liver disease (ALD) and a high incidence of morbidity and mortality. Alcoholic fatty liver disease (AFLD), the earliest stage of ALD, is a multifactorial injury that involves oxidative stress and disruptions of lipid metabolism. Although benign and reversible, no pharmacological treatments are available for this condition. In the present study, we induced AFLD in mice with 10% ethanol and a low-protein diet and then orally treated them with a hydroethanolic extract of Baccharis trimera (HEBT; 30 mg kg-1). HEBT reversed ethanol-induced oxidative stress in the liver, reduced lipoperoxidation, normalized GPx, GST, SOD and Cat activity, and GSH and total ROS levels. The reverser effect of HEBT was observed upon ethanol-induced increases in the levels of plasma and hepatic triglycerides, plasma cholesterol, plasma high-density lipoprotein, and plasma and hepatic low-density lipoprotein. Moreover, HEBT increased fecal triglycerides and reduced the histological ethanol-induced lesions in the liver. HEBT also altered the expression of genes that are involved in ethanol metabolism, antioxidant systems, and lipogenesis (i.e., CypE1, Nrf2, and Scd1, respectively). No signs of toxicity were observed in HEBT-treated mice. We propose that HEBT may be a promising pharmacological treatment for AFLD.

Sydnone 1: A Mesoionic Compound with Antitumoral and Haematological Effects In Vivo.

This study evaluated the antitumour activity of the mesoionic compound sydnone 1 (Syd-1) against Walker-256 carcinosarcoma. Tumour cells were subcutaneously inoculated in the hind limb in male Wistar rats. The animals were orally treated for 12 days with Syd-1 (75 mg/kg) or vehicle. At the end of treatment, considerable decreases in tumour volume and tumour weight were observed in treated animals. Samples of these tumours presented increases in apoptotic bodies and pro-apoptotic protein expression (Bax and p53), while the expression of the anti-apoptotic protein Bcl-2 was reduced. A decrease in reduced glutathione levels and an increase in glutathione peroxidase activity were observed in tumour after Syd-1 treatment. However, significant splenomegaly was evident in animals that received Syd-1, most likely attributable to the induction of haemolysis. This study demonstrated the antitumour activity of Syd-1 against Walker-256 carcinosarcoma. Its mechanism of action is linked to the activation of apoptotic pathways that lead to tumour cell death.

Characterization of an alcoholic hepatic steatosis model induced by ethanol and high-fat diet in rats

Alcoholic liver disease is characterized by a wide spectrum of liver damage, which increases when ethanol is associated with high-fat diets (HFD). This work aimed to establish a model of alcoholic hepatic steatosis (AHS) by using a combination of 10% ethanol and sunflower seeds as the source of HFD. Male rats received water or 10% ethanol and regular chow diet and/or HFD, which consisted of sunflower seeds. The food consumption, liquid intake and body weight of the rats were monitored for 30 days. After this period, blood was collected for biochemical evaluation, and liver samples were collected for histological, mitochondrial enzyme activity and oxidative stress analyses. Our results indicated that the combination of 10% ethanol and HFD induced micro- and macrosteatosis and hepatocyte tumefaction, decreased the levels of reduced glutathione and glutathione S-transferase activity and increased the level of lipoperoxidation and superoxide dismutase activity. The mitochondrial oxidation of NADH and succinate were partially inhibited. Complexes I and II were the main inhibition sites. Hepatic steatosis was successfully induced after 4 weeks of the diet, and the liver function was modified. The combination of 10% ethanol and sunflower seeds as an HFD produced an inexpensive model to study AHS in rats.

Anatomopathology of the superstructure of the stapes in patients with otosclerosis.

Introduction Otosclerosis is a disease that causes bone resorption and deposition in the auditory structures, leading to deafness. Many studies have evaluated the histopathology of the stapes footplate in this disease (osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes), but we found no studies in the literature involving the histology of the superstructure of the stapes. Objectives To perform an analysis under optical microscopy of histopathologic findings of the superstructure of the stapes from patients with otosclerosis. Methods A contemporary cross-sectional cohort study of pathology analysis of superstructures of the stapes of patients with otosclerosis. Results Fifteen superstructures of stapes in patients with otosclerosis operated in our service and four stapes of cadavers used for dissection (controls) were evaluated. No areas of bone resorption or deposition or presence of osteoclasts and osteoblasts in the superstructure of the stapes were found. However, we found in the more distal portions of the crura areas with prominent cementitious lines and woven bone, which was different than the mature trabecular bone found in the head of the stapes or in the controls. Conclusion There were histologic changes in the superstructure of the stapes in patients with otosclerosis operated in our service.

Anatomopathology of the Superstructure of the Stapes in Patients with Otosclerosis

Introduction Otosclerosis is a disease that causes bone resorption and deposition in the auditory structures, leading to deafness. Many studies have evaluated the histopathology of the stapes footplate in this disease (osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes), but we found no studies in the literature involving the histology of the superstructure of the stapes. Objectives To perform an analysis under optical microscopy of histopathologic findings of the superstructure of the stapes from patients with otosclerosis. Methods A contemporary cross-sectional cohort study of pathology analysis of superstructures of the stapes of patients with otosclerosis. Results Fifteen superstructures of stapes in patients with otosclerosis operated in our service and four stapes of cadavers used for dissection (controls) were evaluated. No areas of bone resorption or deposition or presence of osteoclasts and osteoblasts in the superstructure of the stapes were found. However, we found in themore distal portions of the crura areas with prominent cementitious lines and woven bone, which was different than the mature trabecular bone found in the head of the stapes or in the controls. Conclusion There were histologic changes in the superstructure of the stapes in patients with otosclerosis operated in our service. .

Sesquiterpene lactones of Moquiniastrum polymorphum subsp. floccosum have antineoplastic effects in Walker-256 tumor-bearing rats.

BACKGROUND AND AIM: This study aimed to evaluate the in vivo antitumor actions and toxicity of the dichloromethane fraction (F1B) of Moquiniastrum polymorphum subsp. floccosum (formerly Gochnatia polymorpha ssp. floccosa), composed of sesquiterpene lactones, against Walker-256 carcinosarcoma in rats. METHODS: Male Wistar rats received 100 mg kg(-1) F1B per day orally for 16 days after subcutaneous inoculation of Walker-256 cells in the pelvic limb. The tumor progression was monitored, and after treatment, tumor weight, oxidative stress, plasma biochemistry, inflammatory parameters, gene expression and histology of tumor and/or liver were evaluated. The toxicity of F1B was analyzed through the relative weight of organs. Additionally, an LD50 test was performed in mice. RESULTS: F1B treatment significantly reduced tumor volume and weight. There was no difference in oxidative stress in tumor tissue after treatment. F1B treatment modified hepatic glutathione and superoxide dismutase, and normalized plasma glucose, alkaline phosphatase, and amylase. F1B did not affect the activity of myeloperoxidase and N-acetylglucosaminidase or the nitric oxide levels in tumor tissue. However, F1B decreased the tumor necrosis factor (TNF)-α levels. Additionally, F1B increased apoptosis in the tumor, mediated by up-regulation of the p53 and Bax gene expression. No clinical signs of toxicity or death were observed in the rats treated with F1B. The LD50 calculated for mice was 1209 mg kg(-1). CONCLUSIONS: F1B, which is rich in sesquiterpene lactones, showed antitumor activity against Walker-256 carcinosarcoma. This effect may be, at least in part, related to the induction of apoptosis and inhibition of TNF-α signaling.

Clinical-pathological and p53 protein expression study in dysplasia associated with ulcerative colitis / Estudo clínico-patológico e da expressão da proteína p53 nas displasias associadas à retocolite ulcerativa

Background: The association between ulcerative colitis and adenocarcinoma determined strategies for patient follow-up and early detection of dysplastic and neoplastic lesions. Aims: To analyze the incidence of dysplasia in patients with ulcerative colitis, comparing clinical data of patients with and without dysplasia and check immunohistochemical expression of p53 protein in dysplasias. Materials and methods: We analyzed biopsy samples and clinical data of 124 patients with ulcerative colitis at Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil. Results: Dysplasia incidence was low (9.67%) and all cases with low-grade dysplasia. Patients clinical data comparison with and without dysplasia did not show significant statistical differences with regard to the race, age at the start of the disease, age at last biopsy, duration and anatomic extent of ulcerative colitis. Significant difference was found between males and females with predominance of males (58.34%) for dysplasia. Seventeenth biopsy samples of 12 patients with dysplasia, 5 (29.4%) were p53 positive. Conclusions: From these results it is concluded that the incidence of dysplasia was low, higher in males and there was positivity of p53 protein in dysplasia. .

Racional: A associação entre retocolite ulcerativa e adenocarcinoma determinou estratégias para seguimento dos pacientes e detecção precoce das lesões displásicas e neoplásicas. Objetivos: Analisar a incidência de displasia nos pacientes com retocolite ulcerativa, comparar dados clínicos dos pacientes com e sem displasia e verificar a expressão imunoistoquimica da proteína p53 nas displasias. Material e Métodos: Foram estudados os exames anatomopatológicos e dados clínicos de 124 pacientes com e sem displasia, portadores de retocolite ulcerativa no Hospital de Clínicas da Universidade Federal do Paraná. Resultados: A incidência de displasia foi de 9,67% e todos os casos foram de displasia de baixo grau. Na comparação dos dados clínicos dos pacientes com e sem displasia não houve diferença estatisticamente significativa com relação à cor, idade no início da doença, idade na última biópsia, extensão da doença e tempo de evolução da doença. Houve diferença estatística com predomínio de pacientes do sexo masculino (58,34%) em relação ao feminino para displasia. Dos 17 exames avaliados de 12 pacientes com displasia, em 5 exames (29,4%) a expressão da proteína p53 foi positiva. Conclusões: Desses resultados conclui-se que a incidência de displasia foi baixa, maior no sexo masculino e houve positividade da proteína p53 nas displasias. .

Padronização e quantificação de critérios histopatológicos melhoram o diagnóstico da doença intestinal inflamatória? / Do standardization and quantification of histopathological criteria improve the diagnosis of inflammatory bowel disease?

Introduction: Inflammatory bowel disease comprises two major categories: Crohn's disease and ulcerative rectocolitis, both with different clinical and histological aspects, causing sometimes significant morbidity. Objectives: Choose and apply standardized and quantified histopathological diagnosis method, and compare the results and quality index with the original diagnosis. Materials and methods: 43 histological colonoscopic biopsies of 37 patients were re-evaluated by standardized system. Results and discussion: The original diagnoses were more inconclusive (23.3%) than those standardized (2.3%). The agreement with gold standard (clinical, colonoscopical, and radiological diagnosis) was higher on standardized diagnoses (95.3%) than in original (74.4%), especially in relation to Crohn's disease, which percentages were 92.3% and 46.1%, respectively. The quality index was calculated in conclusive diagnosis of each method. For ulcerative rectocolitis, both methods showed sensitivity and negative predictive value of 100%; otherwise the original diagnosis demonstrated specificity of 85.7%, positive predictive value of 96.3% and accuracy of 97.0%, and the standardized diagnosis 92.3%, 96.7% and 97.6%, respectively. For Crohn's disease, there is specificity and positive predictive value of 100% in both methods; the original diagnosis showed sensitivity of 85.7%, negative predictive value of 96.3% and accuracy of 97%, while for the standardized diagnoses 92.3%, 96.7%, and 97.6%, respectively. Conclusion: The standardized diagnosis presented a higher percentage of correct and conclusive diagnoses than those presented in the original diagnosis, especially for Crohn's disease, as well as equal or slightly higher values in some quality index...

Introdução: Duas são as formas de manifestação da doença intestinal inflamatória: doença de Crohn e retocolite ulcerativa, ambas com evolução clínica, tratamento e aspectos histopatológicos diferentes, causando, por vezes, significativa morbidade. Objetivos: Escolher e aplicar método padronizado e quantificado de diagnóstico histopatológico e comparar os resultados e os índices de qualidade, com os dos diagnósticos originais. Materiais e métodos: Foram reavaliadas histologicamente 43 biópsias colonoscópicas seriadas de 37 pacientes por sistema padronizado. Resultado e discussão: Os diagnósticos originais foram mais inconclusivos (23,3%) do que os padronizados (2,3%). A concordância com o padrão-ouro (diagnóstico clínico, colonoscópico e radiológico) foi maior nos diagnósticos padronizados (95,3%) do que nos originais (74,4%), principalmente em relação à doença de Crohn, cujos percentuais foram de 92,3% e 46,1%, respectivamente. Para retocolite ulcerativa, ambos os métodos apresentaram sensibilidade e valor preditivo negativo de 100%; já nos diagnósticos originais, foram verificados especificidade de 85,7%, valor preditivo positivo de 96,3% e acurácia de 97%, e nos diagnósticos padronizados, 92,3%, 96,7% e 97,6%, respectivamente. Para doença de Crohn, verificaram-se especificidade e valor preditivo positivo de 100% nos dois métodos; nos diagnósticos originais, sensibilidade de 85,7%, valor preditivo negativo de 96,3% e acurácia de 97%, e nos diagnósticos padronizados, 92,3%, 96,7% e 97,6%, respectivamente. Conclusão: O diagnóstico padronizado apresentou maior percentual de diagnósticos corretos e conclusivos do que os apresentados no diagnóstico original, principalmente para doença...

The FXR agonist 6ECDCA reduces hepatic steatosis and oxidative stress induced by ethanol and low-protein diet in mice.

BACKGROUND AND AIM: Excessive ethanol consumption can lead to development of hepatic steatosis. Since the FXR receptor regulates adipose cell function and liver lipid metabolism, the aim of this work was to examine the effects of the FXR agonist 6ECDCA on alcoholic liver steatosis development and on oxidative stress induced by ethanol consumption. METHODS: Swiss mice (n=24) received a low-protein diet (6%) and a liquid diet containing 10% ethanol or water for 6weeks. In the last 15days mice received oral treatment with 6ECDCA (3mgkg(-1)) or 1% tween (vehicle). The experimental groups (n=6) were: water+tween, water+6ECDCA, ethanol+tween and ethanol+6ECDCA. Moreover, as a diet control, we used a basal group (n=6), fed by a normal-proteic diet (23%) and water. After the treatment period, the animals were anesthetized for sample collection to perform plasma biochemistry assays, hepatic oxidative stress assays, hepatic cholesterol and triglycerides measurements, liver histology and hepatic gene expression. RESULTS: Ethanol associated with low-protein diet induced hepatic oxidative stress, increased plasma transaminases and induced hepatic lipid accumulation. Many of these parameters were reversed by the administration of 6ECDCA, including amelioration of lipid accumulation and lipoperoxidation, and reduction of reactive oxygen species. These effects were possibly mediated by regulation of Srebpf1 and FAS gene expression, both reduced by the FXR agonist. CONCLUSIONS: Our data demonstrated that 6ECDCA reverses the accumulation of lipids in the liver and decreases the oxidative stress induced by ethanol and low-protein diet. This FXR agonist is promising as a potential therapy for alcoholic liver steatosis.