Journals
2013 EN
Rosana C.L. Salvador · Talita Mm Raposo · Carlos Eduardo FonsecaAlves
+3 more
Background c-KIT is a proto-oncogene that synthesizes a tyrosine kinase protein responsible for cell growth. Higher expression of c-KIT protein in women normal breasts correlates with differentiation status of normal breast epithelium, while loss of c-KIT expression is observed during progression or malignant transformation of mammary epithelium. In bitches the role of this tyrosine kinase receptor has not been established. The aim of this study was to identify c-KIT protein expression in canine breast tissue and compared results with c-KIT expression status in human breast tissue.
Journals
2013 EN
Talita MM Raposo · Carlos Eduardo FonsecaAlves · Érika Maria Terra
+3 more
Background Ataxia telangiectasia mutated (ATM) synthesizes a protein kinase known as a major regulator of DNA damage response. ATM mutations in women have been associated with moderate risk to develop familial Breast Cancer. ATM transcript and protein down-regulation have been reported in sporadic breast carcinomas and the absence of ATM protein expression was also significantly associated with distant metastasis in women. Canine mammary tumors have an incidence three times higher than women and their biological behavior is similar in both species. The aim of this study was to identify the ATM protein expression in canine breast and compared the results with what occurs in women.
Journals
2013 EN
Ana Carolina Inhasz Kiss · Barbara Woodside · Yuri Karen Sinzato
+4 more
Background Neonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood. Methods At birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n = 10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n = 6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p < 0.05 for all data. Results As expected neonatal STZ treatment caused hyperglycemia and hypoinsulinemia in adulthood. STZ-treated pups also showed a temporary reduction in growth rate that probably reflected the early loss of circulating insulin. Hyperglycemic rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered. Conclusions In female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels.
Journals
2013 EN
Magda Luzia Neves · Letícia Yamasaki · Osimar de Carvalho Sanches
+11 more
Background The objective of this study was to evaluate the effectiveness of various linseed oil (LO) preparations (oral, topical, oral and topical combined) in treating experimentally induced keratoconjunctivitis sicca (KCS) in rabbits. Twenty male New Zealand white rabbits were divided into four groups: group C (control), group OLO (oral LO), group TLO (topical LO), and group OTLO (oral and topical LO). The animals were evaluated weekly using Schirmer's tear test (STT), fluorescein test (FT), and Rose Bengal test (RBT) and were euthanized at the end of the experiment for histopathological analysis. Findings There were significant improvements in the parameters analyzed (STT, FT, and RBT) and in the histopathological finding in all of the groups using LO. Conclusions The analyzed results demonstrate that LO, administered orally or topically, was effective in treating experimentally induced KCS in rabbits, although combined oral and topical LO did not show additional benefits greater than those with a single route of administration.
Journals
2013 EN
Pollyanna Santos da Silveira · Ana Luísa Marlière Casela · Érika Pizziolo Monteiro
+5 more
Self-stigma represents a barrier in finding appropriate treatment services, and brings several negative consequences for the individual and the worsening of the situation. Considering that substance dependence is one of the most stigmatizing health conditions, this study aims to assess self-stigma among crack, alcohol, and both substances (crack and alcohol) dependents. The instruments used were: 1) sociodemographic questionnaire to describe participants’ characteristics; the Internalized Stigma of Mental Illness (ISMI) scale adapted for substance users to assess self-stigma; 3) MINI to confirm the substance dependence diagnosis. The sample was composed by 461 patients divided into three groups: 165 alcohol dependents, 141 crack dependents, and 155 crack and alcohol dependents. Most participants were male (91.4%), unemployed (68.6%), and single (70.5%), with incomplete elementary school education (53.3%), with a mean age of 35.38 years. Regarding to involvement in illicit activities, 56.8% stated they were not involved with this type of activity. Comparing self-stigma among the groups investigated, it was found a significant difference between the groups regarding the ISMI overall scores. Similarly, ISMI subscales Alienation, Discrimination Experience, Social Withdrawal and Stigma Resistance also showed a significant difference between groups. On the other hand, the degree of agreement with stereotypes measured by the Stereotype Endorsement subscale did not differ between the groups investigated. The negatives stereotypes associated with substance dependence are equally endorsed and internalized by all groups, however this study showed evidence that crack dependents internalize more negative evaluations related to their condition, and therefore are less likely to seek treatment and adhere to it. The results pointed out the need to consider the impact of stigma on prevention and treatment strategies, in order to encourage patients to seek help and ensure the benefits of interventions. Funding: Fapesp, Capes, CNPQ.
Journals
2013 EN
Mori Akio · Abe Akemi · Kouyama Satoshi
+14 more
Steroid responsiveness of peripheral blood T cells derived from steroid sensitive, steroid dependent, and steroid resistant asthmatics, and induction of steroid resistance by costimulatory signal Akio Mori, Akemi Abe, Satoshi Kouyama, Miyako Yamaguchi, Yo Iijima, Chihiro Mitsui, Chiyako Oshikata, Hidenori Tanimoto, Kiyoshi Sekiya, Takahiro Tsuburai, Masami Taniguchi, Mamoru Ohtomo, Yuji Maeda, Maki Hasegawa, Kazuo Akiyama, Takayuki Ohtomo, Osamu Kaminuma
Journals
2013 EN
Masasuke Ohno · Takayuki Ohkuri · Akemi Kosaka
+4 more
Background Expression of miR-17-92 enhances T-cell survival and interferon (IFN)-γ production. We previously reported that miR-17-92 is down-regulated in T-cells derived from glioblastoma (GBM) patients. We hypothesized that transgene-derived co-expression of miR17-92 and chimeric antigen receptor (CAR) in T-cells would improve the efficacy of adoptive transfer therapy against GBM. Methods We constructed novel lentiviral vectors for miR-17-92 (FG12-EF1a-miR-17/92) and a CAR consisting of an epidermal growth factor receptor variant III (EGFRvIII)-specific, single-chain variable fragment (scFv) coupled to the T-cell receptor CD3ζ chain signaling module and co-stimulatory motifs of CD137 (4-1BB) and CD28 in tandem (pELNS-3C10-CAR). Human T-cells were transduced with these lentiviral vectors, and their anti-tumor effects were evaluated both in vitro and in vivo . Results CAR-transduced T-cells (CAR-T-cells) exhibited potent, antigen-specific, cytotoxic activity against U87 GBM cells that stably express EGFRvIII (U87-EGFRvIII) and, when co-transduced with miR-17-92, exhibited improved survival in the presence of temozolomide (TMZ) compared with CAR-T-cells without miR-17-92 co-transduction. In mice bearing intracranial U87-EGFRvIII xenografts, CAR-T-cells with or without transgene-derived miR-17-92 expression demonstrated similar levels of therapeutic effect without demonstrating any uncontrolled growth of CAR-T-cells. However, when these mice were re-challenged with U87-EGFRvIII cells in their brains, mice receiving co-transduced CAR-T-cells exhibited improved protection compared with mice treated with CAR-T-cells without miR-17-92 co-transduction. Conclusion These results warrant the development of novel CAR-T-cell strategies that incorporate miR-17-92 to improve therapeutic potency, especially in patients with GBM.
Journals
2013 EN
Chikako Shibata · Motoyuki Otsuka · Takahiro Kishikawa
+4 more
Expanding knowledge about the crucial roles of microRNAs (miRNAs) in human diseases has led to the idea that miRNAs may be novel, promising therapeutic targets against various pathological conditions. The recent success of a human clinical trial using anti-miR-122 oligonucleotides against chronic hepatitis C virus has paved the way for this approach. In this review, we summarize briefly the current status of clinical trials of miRNA-targeting therapy and several representative preclinical trials against hepato-gastrointestinal carcinoma. In addition, we describe the currently available technologies for modification and delivery of oligonucleotides, which are essential in providing efficient, specific and safe approaches to targeting miRNAs.
Journals
2013 EN
Akemi Uchida · Satoru Ito · Bélâ Suki
+2 more
The forced oscillation technique (FOT) is a useful tool to assess respiratory resistance and reactance during tidal breathing in patients with respiratory diseases, specifically asthma and chronic obstructive pulmonary disease. Although the FOT has been clinically used, results of respiratory impedance can be affected by various factors such as upper airway artifact. We investigated the effects of cheek support on respiratory resistance and reactance measured by a commercially available FOT equipment MostGraph-01. Respiratory resistance at 20 Hz (R20) with support of the cheeks was significantly higher than those without the cheek support in healthy subjects. Two different cheek support protocols, support of the cheeks by subjects themselves and an operator, were compared in healthy volunteers and patients with respiratory diseases. The cheek support protocols significantly affected respiratory resistance at 5 Hz (R5) and reactance at 5 Hz (X5) in the patient group but not in the healthy subjects. Moreover, for X5, there was a significant interaction between cheek support protocols (by a subject or operator) and groups (healthy or diseased). In conclusion, during impedance measurements using the FOT, application of cheek support either by subjects or the operator is recommended to reduce upper airway artifacts, however, results obtained by two protocols may be different in patients with respiratory diseases. Contribution of the chest wall and position of the arms to the mechanical properties should be carefully considered in physiological studies in which the FOT is attempted.
Springer International Publishing
Journals
2013 EN
Samuele Cortese · Stephen V. Faraone · Silvia Bernardi
+2 more
A significant association between attention-deficit hyperactivity disorder (ADHD) and obesity has been reported. This study addresses unexplored aspects of this relationship.
Cambridge University Press