The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

Refluxo gastroesofágico em cadelas durante ovário-histerectomia convencional submetidas a diferentes medicações pré-anestésicas / Gastroesophageal reflux in dogs undergoing conventional ovariohysterectomy using different premedications

A doença do refluxo gastroesofágico decorre do fluxo de conteúdo gastroduodenal para o esôfago e/ou para os órgãos adjacentes, o que leva à ampla gama de sinais e implicações clínicas. É desconhecida a incidência de refluxo gastroesofágico transoperatório em caninos. O objetivo deste trabalho foi, por meio da endoscopia flexível, avaliar a presença do refluxo gastroesofágico em cadelas submetidas a ovário-histerectomia com base nos fármacos analgésicos utilizados na medicação pré-anestésica (morfina, tramadol ou metadona). Concluiu-se que não houve diferença na incidência de refluxo gastroesofágico transoperatório, não tendo os fármacos testados influenciado de forma diferente esse comportamento; porém, alguns animais do grupo morfina apresentaram êmese pré-operatória. A gravidade dos refluxos foi maior nas cadelas submetidas ao uso da metadona, de acordo com o método de avaliação utilizado para esta pesquisa.(AU)

Gastroesophageal reflux disease arises from the gastroduodenal content flow to the esophagus and/or associated organs, which leads to the wide range of signs and clinical implications. Incidence of intraoperative gastroesophageal reflux disease in dogs is unknown. The objective was, through flexible endoscopy, to assess the presence of gastroesophageal reflux in dogs undergoing ovariohysterectomy based on analgesic drugs used in premedication (morphine, tramadol or methadone). It was concluded that there was no difference in the incidence of intraoperative gastroesophageal reflux, these drugs don't influence this behavior; however, in the morphine group some animals showed preoperative vomiting. The severity of the reflux was higher, but not significantly, in bitches undergoing the methadone according to the evaluator method used for this research.(AU)

Caracterização físico-química de amostras de mel de abelha africanizada dos municípios de Santa Helena e Terra Roxa (PR) / Physicochemical parameters of honey from samples from africanized honeybees in Santa Helena and terra roxa counties (PR)

O presente estudo teve como objetivo a caracterização físico-química de amostras de mel de Apis mellifera coletadas nos municípios de Santa Helena e Terra Roxa, localizados na região oeste do Estado do Paraná, Brasil. Foram coletadas 40 amostras de mel, sendo 20 do município de Santa Helena e 20 de Terra Roxa (PR), coletadas diretamente com os apicultores, as quais foram submetidas a análises físico-químicas de umidade, acidez, pH, cinzas, condutividade elétrica e cor, a fim de verificar se as mesmas apresentavam-se em conformidade com a legislação nacional vigente (Instrução Normativa nº 11), além de conhecer o perfil físico-químico do mel das diferentes localidades, na safra 2008/2009. Os dados encontrados foram submetidos à análise de variância e teste F a 5% de significância. Os resultados apresentaram diferença significativa (P<0,05) apenas entre os valores de acidez, tendo o mel oriundo de Terra Roxa apresentado valor mais alto (33,45±7,7meq.kg-1) que o de Santa Helena (24,53±6,3meq.kg-1). Em sua maioria, as amostras analisadas encontraram-se dentro das especificações determinadas pela legislação para as características físico-químicas, com exceção do parâmetro de umidade, que, apesar de não ter apresentado diferença significativa entre os valores encontrados para os dois municípios, estavam acima do limite estabelecido pela legislação (20 por cento) em 8 amostras do município de Santa Helena e em 7 de Terra Roxa, totalizando 37,5 por cento) das amostras. Essa característica pode ter deixado o produto mais susceptível à fermentação e pode ter sido ocasionada pela colheita imatura do mel...

This study aimed to physicochemically characterize the honey samples of Apis mellifera collected in Santa Helena and Terra Roxa counties, located in the western region of Paraná State, Brazil. Forty honey samples were collected, 20 in Santa Helena and 20 in Terra Roxa (PR) counties, directly from beekeepers, and were subjected to physico-chemical analyzes of moisture, acidity, pH, ashes, electrical conductivity and color, to verify whether they were in accordance with the existing national legislation (Instruction No. 11), in addition to knowing the physicochemical profile of different sites during the 2008/2009 season. The data were submitted to analysis of variance and F test at 5 percent significance level. The results showed significant differences (P<0.05) between values of acidity, and the honey samples from Terra Roxa presented a higher value (33.45±7.7 meq.kg-1) than Santa Helena (24 = 53±6.3 meq.kg-1). Most of the analyzed samples were within the specifications prescribed in the legislation for the physico-chemical parameters except for moisture, which despite having presented a significant difference between values obtained from two counties, were above the limits established by the legislation (20 percent) in eight samples in Santa Helena and seven in Terra Roxa counties, totaling 37.5 percent. This characteristic may have made the product more susceptible to fermentation, and may have been caused by harvesting immature honey...

Rendimiento productivo y características de la canal de corderos alimentados con dietas con diferentes niveles de torta de palma / Productive performance and carcass characteristics of lambs fed diets containing different levels of palm kernel cake

Objective. The objective of this study was to determine the effect on productive performance and carcass characteristics in lambs fed with different amounts of palm kernel cake. Material and methods. Thirty-two Santa Inês lambs, with an initial live body weight of 24.8 ± 3.59 kg were used. Treatments consisted of four levels (0; 6.5; 13.0 and 19.5%) of palm kernel cake added to the dry matter diet. Lambs were fed for 80 days, and then slaughtered to be evaluated for the quantitative characteristics of the carcass. Results. Intake of dry matter and non-structural carbohydrates decreased with increasing levels of palm kernel cake. The intake of neutral detergent fiber showed a linear increase. Crude protein and total digestive nutrient intake were not affected. Weight gain, and the feed:gain ratio of dry matter, organic matter, crude protein and total digestive nutrients were similar among the four treatments. There was an increase on the feed:gain ratio of neutral detergent fiber and a decrease of nonstructural carbohydrates. The weight gain at slaughter and biometric measures were not affected by treatment. The carcass compactness index showed a linear decrease. The indexes of leg muscularity, compactness of the leg and rib eye area were similar among treatments. There was a linear decrease in the cold carcass weight and commercial yield of the carcass. Conclusions. The diet made of up to 19.5% palm kernel cake reduced DM intake, the carcass compactness index and carcass commercial yield, but did not alter weight gain, or feed dry matter intake.

Micronuclei as biomarkers for evaluating the risk of malignant transformation in the uterine cervix.

We evaluated micronucleus and apoptosis occurrence among women with normal smears and women with different kinds of cervical abnormalities, i.e., inflammatory processes and low- and high-grade squamous intraepithelial lesions (N = 12, N = 10 and N = 27, respectively). The sample included 59 women who were seen at a public medical service for cervical cancer prevention in Feira de Santana, Bahia, Brazil. The diagnosis was established by means of cytological, colposcopic, and histopathological examination. Cytogenetic analysis was performed on 2000 cells from each woman and included assessment of micronuclei and nuclear degenerative abnormalities indicative of apoptosis (karyorrhexis, pyknosis and condensed chromatin). Micronucleus frequency was significantly higher in the women with high-grade squamous intraepithelial lesions than in the women without cervical abnormalities or inflammatory processes (P< 0.001) or in the women with low-grade squamous intraepithelial lesions (P < 0.005). The frequency of apoptosis was similar in women without cervical abnormalities and women showing high-grade squamous intraepithelial lesions (P > 0.50), and significantly lower in women without cervical abnormalities and in women showing high-grade squamous intraepithelial lesions than in women showing inflammatory processes or low-grade squamous intraepithelial lesions (P < 0.0001). These results indicate that, in addition to Papanicolaou cervical cytological analysis, it would be useful to use micronucleus analysis to screen women who are at risk of developing cervical cancer. The assessment of nuclear degenerative abnormalities indicative of apoptosis increased the sensitivity of this test.

Genetic correlations between categorical morphological traits in Nelore cattle by applying Bayesian analysis under a threshold animal model.

In this study, Bayesian analysis under a threshold animal model was used to estimate genetic correlations between morphological traits (body structure, finishing precocity and muscling) in Nelore cattle evaluated at weaning and yearling. Visual scores obtained from 7651 Nelore cattle at weaning and from 4155 animals at yearling, belonging to the Brazilian Nelore Program, were used. Genetic parameters for the morphological traits were estimated by two-trait Bayesian analysis under a threshold animal model. The genetic correlations between the morphological traits evaluated at two ages of the animal (weaning and yearling) were positive and high for body structure (0.91), finishing precocity (0.96) and muscling (0.94). These results indicate that the traits are mainly determined by the same set of genes of additive action and that direct selection at weaning will also result in genetic progress for the same traits at yearling. Thus, selection of the best genotypes during only one phase of life of the animal is suggested. However, genetic differences between morphological traits were better detected during the growth phase to yearling. Direct selection for body structure, finishing precocity and muscling at only one age, preferentially at yearling, is recommended as genetic differences between traits can be detected at this age.

The human digastric muscle: patterns and variations with clinical and surgical correlations.

The digastric muscle is located in the suprahyoid region on each side and frequently exhibits two muscular bellies (anterior and posterior) linked by an intermediate tendon. The paired digastric muscles act together either depressing the mandible or elevating the hyoid bone; therefore acting as a single muscle with important physiological roles. In the present study, the digastric muscle has been analyzed bilaterally in 74 adult human cadavers. A computerized morphometrical investigation of the digastric muscles has been performed (Image Pro Plus software package, Media Cybernetics, USA) and the resulting quantitative data have been statistically assessed (SPSS 11.0 for Windows, USA). We hereby propose an original morphological classification that encompasses five types (I-V) for the anterior belly (AB); three types (I-III) for the intermediate tendon (IT); and two types (I-II) for the posterior belly (PB) of the human digastric muscle. In each digastric muscle, the aforementioned anatomical types have been characterized according to the muscular bellies and intermediate tendon. Consequently, as a result of the combinations of those diverse types, individual digastric muscles have been considered as pertaining to distinctive morphological patterns (named from A to J). Cases with absence of either AB or PB have been included in patterns K and L and would be more appropriately defined as monogastric muscles. This innovative classification provides clear-cut anatomical parameters for interpreting morphological variants of the digastric muscle with relevant clinical and surgical correlations.

Experimental chronic entrapment of the sciatic nerve in adult hamsters: an ultrastructural and morphometric study

Entrapment neuropathy is a group of clinical disorders involving compression of a peripheral nerve and interference with nerve function mostly through traction injury. We have investigated the chronic compression of peripheral nerves as an experimental procedure for detecting changes in ultrastructural nerve morphology. Adult hamsters (Mesocricetus auratus, N = 30) were anesthetized with a 25 percent pentobarbital solution and received a cuff around the right sciatic nerve. Left sciatic nerves were not operated (control group). Animals survived for varying times (up to 15 weeks), after which they were sacrificed and both sciatic nerves were immediately fixed with a paraformaldehyde solution. Experimental nerves were divided into segments based upon their distance from the site of compression (proximal, entrapment and distal). Semithin and ultrathin sections were obtained and examined by light and electron microscopy. Ultrastructural changes were qualitatively described and data from semithin sections were morphometrically analyzed both in control and in compressed nerves. We observed endoneurial edema along with both perineurial and endoneurial thickening and also the existence of whorled cell-sparse structures (Renaut bodies) in the subperineurial space of compressed sciatic nerves. Morphometric analyses of myelinated axons at the compression sites displayed a remarkable increase in the number of small axons (up to 60 percent) in comparison with the control axonal number. The distal segment of compressed nerves presented a distinct decrease in axon number (up to 40 percent) comparatively to the control group. The present experimental model of nerve entrapment in adult hamsters was shown to promote consistent histopathologic alterations analogous to those found in chronic compressive neuropathies

Experimental chronic entrapment of the sciatic nerve in adult hamsters: an ultrastructural and morphometric study.

Entrapment neuropathy is a group of clinical disorders involving compression of a peripheral nerve and interference with nerve function mostly through traction injury. We have investigated the chronic compression of peripheral nerves as an experimental procedure for detecting changes in ultrastructural nerve morphology. Adult hamsters (Mesocricetus auratus, N = 30) were anesthetized with a 25% pentobarbital solution and received a cuff around the right sciatic nerve. Left sciatic nerves were not operated (control group). Animals survived for varying times (up to 15 weeks), after which they were sacrificed and both sciatic nerves were immediately fixed with a paraformaldehyde solution. Experimental nerves were divided into segments based upon their distance from the site of compression (proximal, entrapment and distal). Semithin and ultrathin sections were obtained and examined by light and electron microscopy. Ultrastructural changes were qualitatively described and data from semithin sections were morphometrically analyzed both in control and in compressed nerves. We observed endoneurial edema along with both perineurial and endoneurial thickening and also the existence of whorled cell-sparse structures (Renaut bodies) in the subperineurial space of compressed sciatic nerves. Morphometric analyses of myelinated axons at the compression sites displayed a remarkable increase in the number of small axons (up to 60%) in comparison with the control axonal number. The distal segment of compressed nerves presented a distinct decrease in axon number (up to 40%) comparatively to the control group. The present experimental model of nerve entrapment in adult hamsters was shown to promote consistent histopathologic alterations analogous to those found in chronic compressive neuropathies.

Biochemical behaviour of norbixin during in vitro DNA damage induced by reactive oxygen species.

Naturally occurring antioxidants such as carotenoids are extensively studied for their potential in reducing the risk for cancer and other chronic diseases. In the present study, the radical-scavenger activity of the food additive norbixin, a water-soluble carotenoid extracted from Bixa orellana seeds and commercialized as annatto, was evaluated under conditions of DNA damage induced by reactive oxygen species, particularly by hydroxyl radicals. The cell-free scavenger activity of norbixin was evaluated using plasmid DNA as target molecule and Sn2+ or Fe2+ as oxidant. The addition of H2O2 enhanced DNA breakage induced by metal ions, particularly Fe2+. Under these conditions, norbixin started to protect plasmid DNA against single- and double-strand breakage at a metal:norbixin ratio of 1:1 (Sn2+) and 1:10 (Fe2+). However, at lower ratios to Sn2+, norbixin enhanced Sn2+-induced DNA breakage (P < 0.05). The ability of norbixin to protect genomic DNA against oxidative damage was assessed in murine fibroblasts submitted to H2O2-induced oxidative stress and the results were evaluated by the comet assay. Under low serum conditions (2 % fetal bovine serum (FBS)), a protective effect of norbixin against H2O2-induced DNA breakage was inversely related to its concentration, a protection ranging from 41 % (10 microm) to 21 % (50 microm). At higher concentrations of norbixin, however, oxidative DNA breakage was still enhanced, even in the presence of a high serum concentration (10 % FBS). Under normal conditions, norbixin per se has no detectable genotoxic or cytotoxic effects on murine fibroblasts. The antimutagenic potential of norbixin against oxidative mutagens was also evaluated by the Salmonella typhimurium assay, with a maximum inhibition of 87 % against the mutagenicity induced by H2O2. Although plasmid DNA and Ames data indicated that norbixin can protect DNA against oxidative damage, it seems to be a risky guardian of genomic DNA as it can also increase the extent of oxidative damage.

Gallium-67 imaging in a patient with paracoccidioidomycosis: a case report.

A 26 year-old female was admitted with abdominal pain, fever and weight loss. The clinical and laboratory investigations led to the diagnosis of paracoccidioidomycosis. Gallium-67 whole body images correlated well with the clinical course of the disease and with the patient's prognosis.

Evaluation of the level of knowledge about visceral leishmaniasis in endemic areas of Maranhao, brazil

A prospective study was performed to identify knowledge concerning visceral leishmaniasis (VL) in endemic areas of Maranhao, amongst the rural population of the Codo township and in a peripheral urban area (an old settlement, Maracana, on the outskirts of the city of Sao Luis, and Vila Nova/Bom Viver, Paco do Lumiar township). A total of 283 persons were interviewed, including 53 from Maracana, 103 from Vila Nova/Bom Viver, and 127 from Codo. The sites presented favorable conditions for the development and maintenance of VL. Some 93.8% of those interviewed had heard of kala-azar. In Maracana, 50.9% referred to sandflies as responsible for the transmission of VL, while 87.2% knew that dogs are the main link in the epidemiological cycle of the disease. Some 77.8% of those interviewed did not know how to control the disease. As regards manifestations of the disease, they largely associated it with fever, anemia, weight loss, and an enlarged abdomen. Only five individuals knew that Glucantimeis used to treat VL. We conclude that knowledge is poor with regard to all aspects of VL in both the rural and peripheral urban area.

Leishmaniosevisceral (calazar) na Ilha de São Luís, Maranhão, Brasil: evolução e perspectivas / Visceral leishmaniasis (kala-azar) on Ilha de São Luís, Maranhão. Brazil: its evolution and outlook

Leishmaniose visceral (calazar) entrou definitivamente como nosologia importante do Estado do Maranhão, Brasil, a partir de 1982. Desde então, vários autores têm trabalhado o tema do ponto de vista de relatos. No entanto, a parte de diagnóstico, tratamento e controle de cura percorreram caminhos difíceis e sempre preocupou os que estudam a doença que se instalou na Ilha de São Luís a partir da desestabilização dos ecótopos da Lutzomya longipalpis, o transmissor mais importante. Após 1993 a constatação de casos com má resposta ao antimoniato-n-metil glucamina (Glucantime®) veio se somar às outras preucupações. O estudo atual mostra como o Sistema Único de Saúde, através dos seus serviços, atua no controle da doença e conclui sobre a existência de refratariedade ao Glucantime® o que impõe maior vigilância no diagnóstico, tratamento e controle de cura dos pacientes.

Visceral leishmaniasis (kala-azar) was definitively an important disease of the state of Maranhão, Brasil since 1982. Since of then, many authors have been working with this topic in spite of reports. Nevertheless, the aspects of diagnosis, treatment an control of cure went through still hard worried the authors have been studying the disease, that came at São Luís Island since of the destabilization of the ecotopes of Lutzomya longipalpis, most important sandflies bites. After 1993 the constatation of cases with bad response to pentavalent antimonial (Glucantime) comes to add the other worries. This actual trial accost the disease and conclude about an existence of failures to Glucantime being important to have much vigilance in the diagnosis, treatment and control of cure of the patients.

[Visceral leishmaniasis (kala-azar) on Ilha de São Luís, Maranhão. Brazil: its evolution and outlook]. / Leishmaniosevisceral (calazar) na Ilha de São Luís, Maranhão, Brasil: evolução e perspectivas.

Visceral leishmaniasis (kala-azar) was definitively an important disease of the state of Maranhão, Brasil since 1982. Since of then, many authors have been working with this topic in spite of reports. Nevertheless, the aspects of diagnosis, treatment an control of cure went through still hard worried the authors have been studying the disease, that came at São Luís Island since of the destabilization of the ecotopes of Lutzomya longipalpis, most important sandflies bites. After 1993 the constatation of cases with bad response to pentavalent antimonial (Glucantime) comes to add the other worries. This actual trial accost the disease and conclude about an existence of failures to Glucantime being important to have much vigilance in the diagnosis, treatment and control of cure of the patients.