Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membranecamouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe 2 O 4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (t max ), as well as changes in DE and t max due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.
IR-780 iodide is a fluorescent dye with optical properties in the near-infrared region that has applications in tumor detection and photothermal/photodynamic therapy. This multifunctional effect led to the development of theranostic nanoparticles with both IR-780 and chemotherapeutic drugs such as docetaxel, doxorubicin, and lonidamine. In this work, we developed two albumin-based nanoparticles containing nearinfrared IR-780 iodide multifunctional dyes, one of them possessing a magnetic core. Molecular docking with AutoDock Vina studies showed that IR-780 binds to bovine serum albumin (BSA) with greater stability at a higher temperature, allowing the protein binding pocket to better fit this dye. The theoretical analysis corroborates the experimental protocols, where an enhancement of IR-780 was found coupled to BSA at 60 °C, even 30 days after preparation, in comparison to 30 °C. In vitro assays monitoring the viability of Ehrlich ascites carcinoma cells revealed the importance of the inorganic magnetic core on the nanocarrier photothermal−cytotoxic effect. Fluorescence molecular tomography measurements of Ehrlich tumor-bearing Swiss mice revealed the biodistribution of the nanocarriers, with marked accumulation in the tumor tissue (≈3% ID). The histopathological analysis demonstrated strong increase in tumoral necrosis areas after 24 and 72 h after treatment, indicating tumor regression. Tumor regression analysis of nonirradiated animals indicate a IR-780 dose-dependent antitumoral effect with survival rates higher than 70% (animals monitored up to 600 days). Furthermore, an in vivo photothermal therapy procedure was performed and tumor regression was also verified. These results show a novel insight for the biomedical application of IR-780-albumin-based nanocarriers, namely cancer therapy, not only by photoinduced therapy but also by a nonirradiation mechanism. Safety studies (acute oral toxicity, cardiovascular evaluation, and histopathological analysis) suggest potential for clinical translation.
Adenoviruses are a highly important public health issue, since they are among the most persistent and ubiquitous viruses present in water and associated with a variety of clinical manifestations. The aim of this study was to use molecular techniques for the detection of adenovirus in public and recreational water supplies in Goiâ-nia, Brazil. From December 2007 to November 2008 water samples were collected in 5 different sites in 2 lakes and 2 rivers of the city. The samples were filtered in a positively charged nylon membrane, and the DNA was extracted using the phenol-chloroform-isoamyl alcohol method. Semi-nested PCR was used to detect adenovirus DNA, and sequence analysis of the semi-nested PCR products was performed to identify the recovered viruses. Adenovirus DNA was detected in 43% (24 of 54) of samples collected. Considering all examined sites, MP1 presented the highest occurrence of adenovirus (6 positive from 10 collected samples), followed by MP2 (3 positive from 6 collected samples), JL (10 positive from 21 collected samples), VB (3 positive from 9 collected samples), and BB (2 positive from 8 collected samples), respectively. The methodology employed proved to be feasible, fast, low-cost, and suitable to be used as screening approach on adenovirus detection in water for public sanitation companies.
The objective of the present work was to register the first proven cases of human pseudomyiasis due to Eristalis tenax in Goiás State, Brazil, underscoring their clinical manifestations and direct relationship with hygiene. The taxonomic identification of the instars was done according to the descriptions and keys presented by James (1947), Hartley (1961) and Guimarães & Papavero (1999 James (1947), Hartley (1961) e Guimarães & Papavero (1999 Gastrointestinal myiasis caused by the cosmopolitan drone fly Eristalis tenax (Diptera: Syrphidae) is classified as pseudomyiasis, given the biology of the fly and that it occurs in an accidental manner. Its presence, in the surface of the digestive tract is responsible for the pathologic physiology, in general of lesser gravity than that caused by the obligatory or facultative parasites 6 . RESUMO O presente trabalho visa registrar os primeiros casos evidenciados de pseudomiíases humanos por Eristalis tenax no estado de Goiás, Brasil, destacando suas manifestações clínicas e suas relações diretas com os hábitos higiênicos. A identificação taxonômica das larvas foi realizada com base nas descrições e chaves apresentadas porThe genus Eristalis (Linnaeus) was designated commonly as Tubifera (Meigen), and some researchers have also denominated it Eristalomyia. The simple observation of the family rat-tailed maggot (long respiratory siphon) characteristic in larvae instars has incited some researchers to the diagnosis of E. tenax. Though, this is not a pathognomonic characteristic, or exclusive to this species or its genus. Thus, many incorrect records and inaccurate descriptions result from this extrapolation 3 .The larvas of E. tenax are extremely resistant to adverse conditions of pressure, heat and salinity 5 . They live in water polluted by feces, sewage, liquid excrements and organic materials in decomposition, including carcasses. Occasionally they can be found in relatively clean water 3 , however, the occurrence of E. tenax larvae in stagnated waters indicates a high degree of pollution 1 .Gastrointestinal pseudomyiasis presents unspecific symptoms and its clinical aspects vary in agreement with the 186
The goal of this study was to monitor the presence of adenovirus in rivers and lakes used for recreation and as a source for the public water supply in the city of Goiânia, Brazil, in addition to carrying out a correlation analysis of the seasonality of adenovirus gene detection and water quality parameters based on yearly monitoring. We collected 54 water samples from two lakes and two rivers. The samples were concentrated by using a positively-charged membrane, and DNA was extracted by a phenol-chloroform-isoamyl alcohol method, followed by PCR. Adenovirus was detected in 44.4% (24 of 54) of the samples collected. Physicochemical and bacteriological tests were carried out according to water quality monitoring standard procedures. Significant differences over the study period were observed for the presence of adenovirus in water and the values for nitrites, phosphates and fixed and total solids. The occurrence of adenovirus showed a seasonal trend, and significant differences with bacteriological tests were not observed. This is the first study to monitor adenovirus in water sources in the Midwestern Region of Brazil. The results may be useful to generate an eco-epidemiological profile of adenoviruses or even to identify the transmission routes of some neglected diseases, showing the importance in monitoring adenoviruses.
The goal of this study was to standardise and use parasitological and molecular techniques in the analysis and seasonal monitoring of opportunistic protozoa in water from fluvial systems for human usage in the municipality of Goiânia, the capital of the state of Goiás, in the midwestern region of Brazil. We focused on Cryptosporidium sp. Cyclospora cayetanensis, Isopora belli, Microsporidia and Giardia lamblia. Water samples were collected monthly from February 2006 to January 2007 and concentrated using vacuum filtration and a positively charged membrane. Several methods were used to identify the different protozoa of interest. To detect coccidia (Cryptosporidium sp., Isospora belli, and Cyclospora cayetanensis), we used a Kinyoun hotstaining method and a modified Ziehl-Neelsen technique. Enteral microsporidia were detected by a hot-chromotrope technique while a MERIFLUOR ® Cryptosporidium kit was used to confirm the presence of Cryptosporidium sp. Finally, we used PCR to detect Cryptosporidium parvum/hominis. Water is of vital importance to living beings; however, due to anthropic action, several microorganisms are disseminated into aquatic environments. Among them are opportunistic protozoa that infect mainly immunodepressed and immunosuppressed individuals, children and elderly people. These protozoa pose a significant health hazard. Nevertheless, the presence of these pathogens is underestimated because they are not considered during routine environmental monitoring. In our study, we were able to observe the presence of Giardia cysts, Cryptosporidium sp. and Cryptosporidium parvum oocysts in the bodies of water monitored in this research.
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