Melatonin bioengineered: A New Possible Strategy for Treatment of Breast Cancer

Breast cancer is an important public health problem, with an estimated 3.2 million new cases by the year 2050. Diet plays a key role in the etiology of breast cancer and breastfeeding is associated with a lower incidence of breast cancer. On the other hand, the improvement of the therapeutic properties of bioactive compounds through their incorporation into microcarriers is an important strategy in obtaining new therapies, since cyclical changes in concentration are eliminated; there is biological availability of the compound as well as the reduction in toxicity, number dose and suppression of adverse reactions. Studies using hormones such as melatonin extracted from human milk adsorbed onto polyethylene glycol (PEG) microspheres showed that the controlled release of this compound was able to reduce viability and induce apoptosis in MCF-7 cell lines. Colostrum differs from most of the secretions because it contains viable leukocytes during the first days of lactation with a quantity and activity comparable to blood leukocytes, and has several defense components such as antibodies and hormones, such as melatonin (MLT). This review details the influence of the soluble and cellular components present in human colostrum, such as the MLT hormone, as the modified release systems influence the action of MLT and the possible mechanisms involved that contribute to the hypothesis of reduction of breast cancer in women who breastfed

Re-engineering Primary Epithelial Cells from Rhesus Monkey Parotid Glands for Use in Developing an Artificial Salivary Gland

There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjögren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na+/K+-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63202/1/ten.2006.12.2939.pd

Sap flow in 'Tommy Atkins' mango trees under regulated deficit irrigation.

Knowledge of transpiration is of fundamental importance for improving irrigation management. This study measured sap flow of the 'Tommy Atkins' mango tree using Granier?s thermal dissipation probe method under regulated deficit irrigation. The work was conducted in a 10-year-old ?Tommy Atkins? mango orchard, irrigated by micro sprinkler, located in the Irrigated Perimeter of Ceraíma, in Guanambi, Bahia, Brazil. Sap flow measurements were carried out on three consecutive days in plants under regulated deficit irrigation, with reductions of 30 and 60% of crop evapotranspiration in three phases of fruit development; beginning of flowering to early fruit growth (Phase I), fruit expansion (Phase II) and physiological maturation of fruits (Phase III). Regulated deficit irrigation led to reduced sap flow in ?Tommy Atkins? mango tree

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.Federal University of São PauloSanta Casa de Misericórdia Gastroenterology ServiceFederal University of ParáFederal University of Juiz de ForaSão Paulo University Medical School of Ribeirão PretoEmílio Ribas InstituteFederal University of Minas GeraisMedical School of São José do Rio PretoFederal University of AlagoasFederal University of Santa CatarinaFederal University of BahiaTropical Medicine FundationOswaldo Cruz HospitalFederal University of ParaíbaRocheUNIFESPSciEL

Anatomical study of the mandibular canal course in felines (Felis catus domesticus)

Objetivou-se descrever, por meio de tomografia computadorizada, o trajeto do canal mandibular (CM) em 20 gatos sem raça definida, com ausência de alterações na cavidade oral, provenientes do Centro de Controle de Zoonoses do Distrito Federal. Foram realizados cortes tomográficos com 2mm de espessura, acompanhando todo o trajeto do CM, tendo como referência a região do forame mandibular, as raízes distais e mesiais dos dentes pré-molares e molares e o forame mentoniano, obtendo-se medidas desde o CM até as faces vestibular, lingual, ventral e alveolar (profundidade) do corpo da mandíbula, bem como seu diâmetro. Pôde constatar que o CM manteve-se no aspecto lingual do corpo da mandíbula desde o forame mandibular até a raiz mesial do 1º pré-molar, onde se deslocou para a face vestibular, emergindo no forame mentoniano. Com relação à profundidade, seu trajeto sofreu declive a partir do forame mandibular até a região da raiz mesial do 1º molar, onde alcançou seu ponto mais profundo para prosseguir em suave ascensão até o forame mentoniano. Os dados apresentados contribuem para o estudo anatômico da mandíbula de gatos, bem como auxiliam no melhor planejamento e execução de procedimentos cirúrgicos na mandíbula dessa espécie.This study aimed to describe the path of the mandibular canal (MC), using computerized tomography, in twenty mongrel cats, with no changes in the oral cavity, from the Zoonosis Control Center of the Federal District. 2mm thick tomographic sections were taken following the entire path of the mandibular canal, considering as reference the region of the mandibular foramen, the distal and mesial roots of premolar and molar teeth, and mental foramen, obtaining measurements from the MC until the buccal, lingual, ventral and alveolar (depth) surfaces of the mandibular body as well as its diameter. MC remained on the lingual aspect of the mandibular body from the mandibular foramen to the mesial root of the first premolar, where it displaced to the buccal surface, emerging from the mental foramen. Regarding the depth, we observed a downward path from the mandibular foramen to the mesial root of the first premolar, where it reached its deepest point, the path continued in gentle ascent until to the mental foramen. Our data contribute to the anatomical study of the feline jaw and allow a better planning and execution of surgical procedures in the mandible of this species

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract\ud \ud \ud \ud Background\ud \ud An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial.\ud \ud \ud \ud Results\ud \ud Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets.\ud \ud \ud \ud Conclusions\ud \ud Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.This work was supported in part by funds from the National Institutes of Health (AI076059 and AI084113). Additional support was provided by the Brazilian Program for STD and AIDS, Ministry of Health (914/BRA/3014 - UNESCO/Kallas), the São Paulo City Health Department (2004–0.168.922-7/Kallas), Fundação de Amparo a Pesquisa do Estado de São Paulo (04/15856-9/Kallas and 2010/05845-0/Kallas and Nixon), the John E. Fogarty International Center (D43 TW00003), and the Fundação de Amparo a Pesquisa do Estado de São Paulo (04/15856-9/Kallas and 2010/05845-0/Kallas and Nixon). RBJ gratefully acknowledges salary support from the Ontario HIV Treatment Network (OHTN)

Participation, knowledge production, and evaluative research: participation by different actors in a mental health study

This article reflects on the interrelations between participation, knowledge production, and public policy evaluation in light of issues from our own experience with evaluative research on a municipal network of Psychosocial Care Centers (CAPS) in Brazil. The article discusses the coordination of the complex process and the potentials and limits of partnerships for conducting qualitative evaluative studies in mental health with participation by different social actors. The authors conclude that qualitative evaluative research aligned with the perspective of including different points of view representing various segments is the best approach for understanding the numerous spin-offs from the implementation of services linked to the Brazilian psychiatric reform movement, given the inherent specificities of the mental health field.No presente texto apresentamos considerações sobre pesquisa avaliativa qualitativa e participativa com base em investigação desta natureza realizada junto a uma rede municipal de Centros de Atenção Psicossocial (CAPS) ligados ao Sistema Único de Saúde (SUS). A coordenação do complexo processo, bem como as potencialidades e limites do estabelecimento de parcerias para a realização de trabalhos de investigação avaliativa qualitativa em saúde mental, com a inclusão de diferentes atores sociais, são aqui discutidas. Concluímos que a pesquisa avaliativa qualitativa aliada à perspectiva de inclusão de distintos pontos de vista dos vários segmentos envolvidos é a que melhor se adequa à compreensão dos muitos desdobramentos oriundos da implementação de serviços ligados ao movimento de reforma psiquiátrica brasileira, dado as especificidades inerentes ao campo da saúde mental.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP)Universidade Estadual de Campinas FCMUNIFESPSciEL