15-deoxy-delta(12,14)-prostaglandin J(2) Induces Apoptosis And Upregulates Socs3 In Human Thyroid Cancer Cells

The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a natural ligand of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and a potential mediator of apoptosis in cancer cells. In the present study, we evaluated the effect of 15d-PGJ(2) in human thyroid papillary carcinoma cells (TPC-1) using different doses of 15d-PGJ(2) (0.6 to 20 mu M) to determine IC50 (9.3 mu M) via the MTT assay. The supernatant culture medium of the TPC-1 cells that was treated either with 15d-PGJ(2) or with vehicle (control) for 24 hours was assessed for IL-6 secretion via CBA assay. RT-qPCR was used to evaluate mRNA expression of IL-6, SOCS1, SOCS3, and STAT3. TPC-1 cells treated with 15d-PGJ(2) decreased the secretion and expression of IL-6 and STAT3, while it increased SOCS1 and SOCS3. Overall, we demonstrated that 15d-PGJ(2) downregulated IL-6 signaling pathway and led TPC-1 cells into apoptosis. In conclusion, 15d-PGJ(2) shows the potential to become a new therapeutic approach for thyroid tumors

Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta

Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid

In Vitro and In Vivo Investigation of the Efficacy of Arylimidamide DB1831 and Its Mesylated Salt Form - DB1965 - against Trypanosoma cruzi Infection

Chagas disease is caused by infection with the intracellular protozoan parasite Trypanosoma cruzi. At present, nifurtimox and benznidazole, both compounds developed empirically over four decades ago, represent the chemotherapeutic arsenal for treating this highly neglected disease. However, both drugs present variable efficacy depending on the geographical area and the occurrence of natural resistance, and are poorly effective against the later chronic stage. As a part of a search for new therapeutic opportunities to treat chagasic patients, pre-clinical studies were performed to characterize the activity of a novel arylimidamide (AIA - DB1831 (hydrochloride salt) and DB1965 (mesylate salt)) against T.cruzi. These AIAs displayed a high trypanocidal effect in vitro against both relevant forms in mammalian hosts, exhibiting a high selectivity index and a very high efficacy (IC50 value/48 h of 5–40 nM) against intracellular parasites. DB1965 shows high activity in vivo in acute experimental models (mouse) of T.cruzi, showing a similar effect to benznidazole (Bz) when compared under a scheme of 10 daily consecutive doses with 12.5 mg/kg. Although no parasitological cure was observed after treating with 20 daily consecutive doses, a combined dosage of DB1965 (5 mg/kg) with Bz (50 mg/kg) resulted in parasitaemia clearance and 100% animal survival. In summary, our present data confirmed that aryimidamides represent promising new chemical entities against T.cruzi in therapeutic schemes using the AIA alone or in combination with other drugs, like benznidazole

Regionalização para o cultivo do feijão no Rio Grande do Sul com base na interação genótipo x ambiente¹.

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A comunicação da suspensão de cirurgias pediátricas: sentimentos dos familiares envolvidos no processo

A hospitalização é uma experiência complexa, sendo agravada no caso de necessidade de intervenção cirúrgica, principalmente quando o paciente é criança. Quando a cirurgia é suspensa, paciente e seus familiares podem apresentar sentimentos de insegurança, angústia e ansiedade. Este estudo teve como objetivo identificar e descrever a percepção de quinze mães e/ou responsáveis por crianças de 0 a 18 anos, internadas em um hospital, após receberem a notícia de que a cirurgia de seu filho foi suspensa. É um estudo descritivo, qualitativo, que utilizou o referencial teórico da Comunicação Interpessoal e o metodológico da Análise de Conteúdo. Os resultados evidenciaram que as suspensões de cirurgias pediátricas são fatos presentes na instituição, que trazem repercussões ao paciente e familiares, e à organização institucional; que a comunicação entre profissionais da saúde, pacientes e familiares é inadequada; que a atuação do enfermeiro na notícia da suspensão da cirurgia precisa ser efetiva.La hospitalización es una experiencia compleja, agravada en el caso de ser necesaria una intervención quirúrgica, en particular cuando el enfermo es un niño. Cuando la cirugía es suspendida, el enfermo y sus familiares pueden manifestar sentimientos de inseguridad, angustia y ansiedad. Este estudio tuve como objetivo identificar e describir la percepción de quince madres y/o responsables por niños con edades entre 0 y 18 años internados en un hospital después de recibir la noticia de que la cirugía de su hijo fue suspendida. Se trata de un estudio descriptivo cualitativo que utilizó el referencial teórico de la Comunicación Interpersonal y la metodología del Análisis de Contenido. Los resultados evidenciaron que las suspensiones de cirugías pediátricas son hechos presentes en la institución, que traen repercusiones al enfermo y familiares y en la propia organización institucional, que la comunicación entre profesionales de la salud, enfermos y familiares es inadecuada y que la actuación del enfermero en la noticia de la suspensión de la cirugía debe ser necesariamente efectiva.Hospitalization is a complex experience; this can be made worse if surgical intervention is required, especially when the patient is a child. When surgery is suspended, patient and family can experience feelings of insecurity, distress, and anxiety. The objective of this study was to identify and describe the perceptions of fifteen mothers or guardians of children between 0 and 18 years old admitted in a teaching hospital, after receiving news that surgery for their child was suspended. This was a descriptive qualitative study which used Interpersonal Communication as theoretical reference and Analysis of Content as the methodology. Results showed that suspension of pediatric surgery in our institution causes repercussions to patients, their families, and institution organisation; that communication between health team professionals, patients and families is inadequate; and that the nurses' participation in informing surgery suspension must be effective

The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

Trypanosoma cruzi is a parasite that causes Chagas disease, which affects millions of individuals in endemic areas of Latin America. One hundred years after the discovery of Chagas disease, it is still considered a neglected illness because the available drugs are unsatisfactory. Aromatic compounds represent an important class of DNA minor groove-binding ligands that exhibit potent antimicrobial activity. This study focused on the in vitro activity of 10 aromatic dicationic compounds against bloodstream trypomastigotes and intracellular forms of T. cruzi. Our data demonstrated that these compounds display trypanocidal effects against both forms of the parasite and that seven out of the 10 compounds presented higher anti-parasitic activity against intracellular parasites compared with the bloodstream forms. Additional assays to determine the potential toxicity to mammalian cells showed that the majority of the dicationic compounds did not considerably decrease cellular viability. Fluorescent microscopy analysis demonstrated that although all compounds were localised to a greater extent within the kinetoplast than the nucleus, no correlation could be found between compound activity and kDNA accumulation. The present results stimulate further investigations of this class of compounds for the rational design of new chemotherapeutic agents for Chagas disease