First report of Kudoa sp. in the palate and pharyngeal musculature of Gobioides grahamae Palmer and Wheeler, 1955 (Perciformes, Gobiidae) from Marajó Island, Brazil / Primeiro registro de Kudoa sp. na musculatura do palato e faringeal de Gobioides grahamae Palmer e Wheeler, 1955 (Perciformes, Gobiidae) da Ilha do Marajó, Brasil

The aim of this study was to describe the first occurrence ofKudoasp. inGobioides grahamae, contributing to the understanding of this group of parasites in the Amazonian ichthyofauna. Forty specimens ofG. grahamaecollected from the natural environment were analyzed. Cysts ofKudoasp. were diffusely distributed through the striated skeletal muscle fibers with severe edema and inflammatory infiltrate composed of lymphocytes were observed in 30% of the specimens. Edema and marked coagulation necrosis of the muscle fibers was associated with infection byKudoasp. spores, which had accumulated inside the skeletal muscle fibers. Although there are no records of foodborne outbreaks caused by Kudoa spp. in Brazil, it is of paramount importance that we evaluate its occurrence, since the consumption of fish, especially raw fish, has increased because of the adoption of Japanese cuisine. To minimize the economic impacts on the fisheries market and the risk of this parasite to public health, it is necessary to initiate a program to monitor the presence of this likely underdiagnosed, emerging parasite.(AU)

O objetivo deste estudo foi descrever a primeira ocorrência de Kudoa sp. em Gobioides grahamae, contribuindo, assim, para a compreensão desse grupo de parasitas na ictiofauna amazônica. Foram analisados 40 espécimes de G. grahamae coletados de ambiente natural. Cistos de Kudoa sp. foram distribuídos difusamente através das fibras musculares esqueléticas estriadas com presença de edema grave e infiltrado inflamatório composto de linfócitos, que foram observados em 30% dos espécimes. Edema e necrose de coagulação acentuada das fibras musculares foram associados com a infecção por esporos de Kudoa sp., acumulados no interior das fibras musculares da faringe. Apesar de não haver registros de surtos de origem alimentar causada por Kudoa spp. no Brasil, é de suma importância a avaliação de sua ocorrência, uma vez que o consumo de peixe, especialmente peixe cru, aumentou por causa da adoção da culinária japonesa. Para minimizar os impactos econômicos no mercado da pesca e o risco desse parasita para a saúde pública, é necessário iniciar um programa para monitorar a presença desse parasita emergente, possivelmente subdiagnosticada.(AU)

Spontaneous multi-cystic peripheral ameloblastoma in the freshwater angelfish, from the Brazilian state of Pará / Ameloblastoma periférico multicístico espontâneo em Acará Bandeira, no Estado do Pará, Brasil

Este trabalho registra a ocorrência espontânea de ameloblastoma em P. scalare. O tumor foi obtido a partir de um exemplar de Acará Bandeira, sendo fixado, seccionado, e os fragmentos processados para microscopia de luz e microscopia eletrônica de varredura (MEV). O exame macroscópico evidenciou uma massa tumoral que se estendia do rebordo alveolar do maxilar superior à face externa labial. À MEV, a neoplasia apresentou uma série de espículas. Microscopicamente, percebia-se um processo neoplásico constituído por tecido conjuntivo de característica mixoide, ricamente vascularizado, onde eram observados fragmentos de tecido osteoide. A amostra revelou proliferação neoplásica do epitélio odontogênico, onde as células neoplásicas se organizavam na forma de paliçada. Alterações histopatológicas em peixes têm sido úteis biomarcadores do efeito à exposição a substâncias tóxicas, sendo as neoplasias lesões específicas, comumente encontradas em peixes de áreas poluídas, revelando uma associação entre as lesões e a exposição a irritantes.(AU)

EMT blockage strategies: Targeting Akt dependent mechanisms for breast cancer metastatic behaviour modulation.

Epithelial Mesenchymal Transition (EMT) is an event where epithelial cells acquire mesenchymal-like phenotype. EMT can occur as a physiological phenomenon during tissue development and wound healing, but most importantly, EMT can confer highly invasive properties to epithelial carcinoma cells. The impairment of E-cadherin expression, an essential cell-cell adhesion protein, together with an increase in the expression of mesenchymal markers, such as N-cadherin, vimentin, and fibronectin, characterize the EMT process and are usually correlated with tumor migration, and metastization. A wide range of micro-environmental and intracellular factors regulate tumor development and progression. The dynamic cross-talk between the adhesion-related proteins such as E-cadherin and the EMT-related transcription factors, with special focus on TWIST, will be discussed here, with the aim of finding a suitable biological pathway to be used as potential target for cancer therapy. Emerging concepts such as the role of the PI3K/AKT/TWIST pathway in the regulation of the E-cadherin expression will be highlighted, since it seems to be consistently involved in cells EMT. The well-known efficacy of the RNA interference as a tool to silence the expression of specific proteins has come into focus as a strategy to control different tumor sub-populations. Despite the oligonucleotides enormous sensitivity and low in vivo stability, new (nano)technological solutions are expected to enable RNAi clinical application in cancer therapy.

Rohdella amazonica n. sp. (Aspidogastrea: Aspidogastridae) from the Amazoninan banded puffer fish Colomesus psittacus (Bloch & Schneider, 1801).

Aspidogastreans are commonly found infecting freshwater and marine molluscs, teleosts fishes and freshwater turtles. The subclass comprises four families - Rugogastridae Schell 1973, Stichocotylidae Faust & Tang 1936, Multicalycidae Gibson & Chinabut 1984 and Aspidogastridae Poche 1907 - and it is characterized by the presence of a ventral adhesive disc divided into rows of alveoli. In the current work, using light and scanning electron microscopy and molecular approaches, a new species of Aspidogastridae of the genus Rohdella Gibson & Chinabut, 1984, is described as a parasite of Colomesus psittacus in Brazil. The new taxon is distinguishable by the presence of oesophageal glands, teguments covered by ciliated papillae, and the position and shape of the hermaphroditic duct. The present work describes the third species of the genus Rohdella, thereby adding new morphological and molecular data regarding Aspidogastridae.

Preclinical development of siRNA therapeutics: towards the match between fundamental science and engineered systems.

The evolution of synthetic RNAi faces the paradox of interfering with the human biological environment. Due to the fact that all cell physiological processes can be target candidates, silencing a precise biological pathway could be challenging if target selectivity is not properly addressed. Molecular biology has provided scientific tools to suppress some of the most critical issues in gene therapy, while setting the standards for siRNA clinical application. However, the protein down-regulation through the mRNA silencing is intimately related to the sequence-specific siRNA ability to interact accurately with the potential target. Moreover, its in vivo biological fate is highly dependent on the successful design of a vehicle able to overcome both extracellular and intracellular barriers. Anticipating a great deal of innovation, crucial to meet the challenges involved in the RNAi therapeutics, the present review intends to build up a synopsis on the delivery strategies currently developed. FROM THE CLINICAL EDITOR: This review discusses recent progress and pertinent limiting factors related to the use of siRNA-s as efficient protein-specific "silencing" agents, focusing on targeted delivery not only to cells of interest, but to the proper intracellular destination.

An anatomopathological study of hepatic coccidiosis (Calyptospora sp. ) in the Acará-pixuna, Aequidens plagiozonatus Kullander, 1984 from the Brazilian state of Pará / Estudo anatomopatológico de coccidiose hepática (Calyptospora sp. ) em Acará-pixuna, Aequidens plagiozonatus Kullander, 1984, no Brasil, estado do Pará

The present study focuses on the anatomopathological alterations provoked by parasitism by Calyptospora sp. in 40 specimens of Aequidens plagiozonatus collected in Pará, Brazil. Examinations of the fresh material by compression of the hepatopancreas and histological sections showed immature forms and oocysts characteristic of the genus Calyptospora, in addition to a large quantity of melanomacrophagic centers spread throughout the organ. No significant inflammation of the hepatic tissue was observed. The melanomacrophagic centers and the compression of the hepatocytes are part of the response of the host to the parasite. This study represents the first record of parasitism by Calyptospora in A. plagiozonatus.

Descreveram-se as alterações anatomopatológicas provocadas pelo parasitismo por Calyptospora sp. em 40 espécimes de Aequidens plagiozonatus, provenientes do município de Peixe-boi, Pará, Brasil. Foram encontradas formas imaturas e oocistos característicos do gênero Calyptospora, nos exames frescos por compressão e cortes histológicos, além de um grande número de centros melanomacrofágicos dispersos por todo o órgão. Digna de nota foi a ausência de inflamação significativa no tecido hepático. Centros melanomacrofágicos e compressão dos hepatócitos estão envolvidos na resposta do hospedeiro ao parasito. Este é o primeiro registro de ocorrência de parasitismo por Calyptospora sp. na espécie estudada.

Biodistribution of lipid nanoparticles: a comparative study of pulmonary versus intravenous administration in rats.

The advent of nanomedicine and increase knowledge on cellular and molecular biology has opened new opportunities on the clinical field. Selective drug targeting and protection of healthy tissues rules the rising interest that is being devoted to drug delivery system strategies, considering that the accurate choice of the carrier molecule will determine the pharmacokinetics and pharmacodynamics of drugs, yielding higher therapeutic efficacy. Despite the improvements in surgery and immunological approaches, tumor staging and cancer therapy remains a challenge, typically because they are ineffective in advanced stages of the disease, but also due to the conventional administration route (intravenous), and consequently the non-specificity of the potentially toxic drugs. The issue currently under the spotlight in drug targeting is the concept of drug delivery systems (DDS) and the impact that is inherent to their selectivity. Moreover, these particulate systems bring forth the possibility of using alternative routes to the conventional intravenous administration. This article reviews the applications of gamma-scintigraphic image technique to evaluate the advances and research on DDS engineering to the pulmonary administration, and the dependency of lung particle removal mechanism on both the administration route and the particulate system characteristic, based on literature data, as well as through the experimental studies performed in our group.

Lymphatic uptake of lipid nanoparticles following endotracheal administration.

A previous publication reported the uptake into the lymphatics of pulmonary administered lipid nanoparticles (LN), after aerosolization and inhalation. In the present study LN clearance from the lungs and lymphatic uptake were further evaluated after endotracheal administration. Nanoparticles prepared with gliceryl behenate were radiolabelled by association to the lipophilic tracer D,L-hexamethylpropylene amine oxime (HMPAO) coupled with 99mTc. Labelling efficiency was 97% and stability in body fluids was demonstrated in vitro. Wistar rats were treated by endotracheal administration and lymphatic uptake was determined upon organ sampling. Endotracheally delivered LN are rapidly eliminated from rat lungs and accumulation in para-aortic, axillary and inguinal lymph nodes starts almost immediately after administration. Translocation of LN across the lung mucosa and their uptake into the lymphatics demonstrate their usefulness as potential drug carriers for lung cancer therapy, as well as for immunization purposes.

Blood lactate removal during recovery at various intensities below the individual anaerobic threshold in triathletes.

AIM: Optimal lactate removal was reported to occur at work-rate between 30% and 70% VO2max. However, it has been recently recommended to quantify exercise intensity not in percentage of VO2max but in relation to validated metabolic reference points such as the individual anaerobic threshold (IAT) and the individual ventilatory threshold (IVT). The purpose of this study was to examine the effect on lactate removal of different recovery work-rates below the IAT defined calculating the difference (DT) between IAT and IVT, then choosing the IVT+50%DT, the IVT and the IVT-50%DT work-rates. METHODS: Eight male triathletes (VO2max 69.7+/-4.7, VO2IAT 52.9+/-4, VO2IVT 41.1+/-4.7 mL x kg(-1) x min(-1)), after a 6-min treadmill run at 75% of difference between IAT and VO2max, performed in a random order the following 30-min recovery treatments: 1) run at IVT(plus;50%DT), 2) at IVT, 3) at IVT(-50%DT), 4) passive. Blood lactate was measured at 1, 3, 6, 9, 12, 15, 20, 25, 30 minutes of recovery. RESULTS: All active recovery work-rates (from 50+/-5% to 67+/-4% VO2max) were within the range previously reported for optimal lactate removal, and significantly more efficient than passive recovery on lactate removal curve (% of accumulated lactate above rest value). However, significant differences (P<0.01) were found among active recovery intensities: the IVT(-50%DT) was the most efficient work-rate from the 9th minute to 30th minute. CONCLUSIONS: In triathletes, the IVT(-50%DT) was the optimal work-rate for lactate removal; moreover none of the studied active work-rate showed further lactate decrease after the 20th minute of recovery.