Development of a rabbit pleural cancer model by using VX2 tumors

Primary and secondary pleural cancer remains an important clinical problem, with research progress limited by the lack of a suitable moderate- to large-sized (3 to 4 kg) animal model of pleural cancer. Many potential pleura-based imaging and treatment modalities cannot be investigated sufficiently by using currently available small murine animal models because their pleural space is not comparable to that of humans and therefore does not allow for the use of standard thoracoscopic techniques. Here we describe the development of a reproducible model of pleural malignancy in moderate-sized immunocompetent rabbits. Under thoracoscopic guidance, 9-15 x 10(6) VX2 carcinoma cells were inoculated into the plural space of 3 to 4 kg New Zealand white rabbits that had undergone gentle pleural abrasion. Malignant tumor involvement developed on the visceral and parietal pleural surfaces in an average of 2 to 4 wk. This novel pleural tumor model induction method likely will facilitate a broad range of investigations of pleural cancer diagnostics and therapeutics.     

Anatomical and chemical characteristics of the seed coat of <i>Medicago sativa</i> L. (alfalfa) cv. Baralfa 85 seeds and their association with seed dormancy

Seeds of alfalfa (Medicago sativa L.) can exhibit seedcoat imposed dormancy, which produces hard seeds within a seed lot. These seeds do not germinate because they do not imbibe water due to a barrier to water entry in the seed coat. The aim of this work was to analyze the anatomical and chemical characteristics of the testa of alfalfa seeds with respect to water permeability levels. The anatomy of seeds of the cv. Baralfa 85 was studied and structural substances, polyphenols, tannins and cutin present in the testa of seeds of different water permeability levels were determined. The anatomical characteristics of the seed coat and the proportions of components were found to determine the permeability level of the seed coat, an aspect that is associated with the physical seed dormancy level. Anatomically, increased thickness of the testa was associated with a lower permeability level. The difference may be attributed to the variation in cuticle thickness, length of macrosclereids and thickness of the cell wall, and presence and development of osteosclereids. From the physiological and chemical points of view, the mechanism of physical dormancy of the testa is explained by a greater amount of components that repel water and cement the cell wall, such as polyphenols, lignins, condensed tannins, pectic substances, and a lower proportion of cellulose and hemicellulose.     

Current medical treatment of estrogen receptor-positive breast cancer

Approximately 80% of breast cancers(BC) are estrogen receptor(ER)-positive and thus endocrine therapy(ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of(1) ovarian function suppression(OFS), usually obtained using gonadotropinreleasing hormone agonists(Gn RHa);(2) selective estrogen receptor modulators or down-regulators(SERMs or SERDs); and(3) aromatase inhibitors(AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs(i.e., tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs(i.e., fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs(i.e., anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors(palbociclib) and mammalian target of rapamycin(m TOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness.     

Rheumatoid factor and anti-citrullinated protein antibody positivity,but not level,are associated with increased mortality in patients with rheumatoid arthritis: results from two large independent cohorts

Introduction

This study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA).

Methods

Data from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment.

Results

A total of 4962 patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. In NOAR and EAC respectively, 35% and 42% of patients were ACPA/RF positive. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% confidence interval) 1.35 (1.09 to 1.68) and 1.58 (1.16 to 2.15).

Conclusions

Patients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0483-3) contains supplementary material, which is available to authorized users.     

Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC₅₀) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC₅₀. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.     

<Emphasis Type="Italic">Escherichia coli</Emphasis> phylogenetic group determination and its application in the identification of the major animal source of fecal contamination

Background  

Escherichia coli strains are commonly found in the gut microflora of warm-blooded animals. These strains can be assigned to one of the four main phylogenetic groups, A, B1, B2 and D, which can be divided into seven subgroups (A₀, A₁, B1, B2₂, B2₃, D₁ and D₂), according to the combination of the three genetic markers chuA, yjaA and DNA fragment TspE4.C2. Distinct studies have demonstrated that these phylo-groups differ in the presence of virulence factors, ecological niches and life-history. Therefore, the aim of this work was to analyze the distribution of these E. coli phylo-groups in 94 human strains, 13 chicken strains, 50 cow strains, 16 goat strains, 39 pig strains and 29 sheep strains and to verify the potential of this analysis to investigate the source of fecal contamination.     

Activity of some Nile River aquatic macrophyte extracts against the cyanobacterium Microcystis aeruginosa

The anti-algal activity of five macrophyte extracts on the cyanobacterium Microcystis aeruginosa in Egypt was investigated in 2013. Extract activity varied according to plant type, extracting solvent and its concentration. The highest inhibitory activity was achieved with ethanol extract at a concentration of 80 mg l^?1, followed by chloroformic extracts, at 60 mg l^?1. Methanolic extracts of Eichhornia crassipes and Polygonum tomentosum inhibited growth of Microcystis aeruginosa at all concentrations. Acetonic extracts inhibited algal growth at 60 mg l^?1, except for the extract of Ceratophyllum subdemersum, which showed stimulation of M. aeruginosa growth. Eichhornia crassipes ethanolic extract exerted the most powerful inhibition by more than five-fold, 570.17%, followed by those of P. tomentosum, Saccharum spontaneum, Ceratophyllum demersum and C. subdemersum, 559.48, 553.99, 544.11 and 366.51%, respectively. Phytochemical screening for the tested plant extracts revealed the presence of biologically active substances of different concentrations, with P. tomentosum having the highest polyphenols, 1.95% of dry weight.     

AChemS: the beginning. Association for Chemoreception Sciences

This paper unfolds the events, the people and the times that led up to the founding of AChemS and fashioned its character during its early formative years. It describes the path over which AChemS came, going from the original assertions and denials for the need of such an organization to its later inception and nascent development. This narration highlights such topics as the debate over the need for AChemS, the role of National Science Foundation in the founding of AChemS, the derivation of the Association's name, the choice of Sarasota and the Hyatt House as the meeting site, the generation of the programs for the early annual meetings, the adoption of the bylaws, the process of incorporation and tax deferment, and the birth of the Givaudan Lectureship. Most emphatically highlighted, however, is the enthusiasm, commitment and hard work that the members of the chemosensory research community displayed in bringing AChemS to fruition.