Selma A.S. Kückelhaus

Antiplasmodial and antileishmanial activities of phylloseptin-1, an antimicrobial peptide from the skin secretion of Phyllomedusa azurea (Amphibia).

The development of drug resistance by infectious agents represents a major hindrance for controlling parasitic diseases and has stimulated the search for new compounds. We have previously shown that phylloseptin-1 (PS-1), a cationic peptide from the skin secretion of Phyllomedusa azurea, exhibited potent antimicrobial activity. Now we evaluate the effect of PS-1 on Leishmania amazonensis and Plasmodium falciparum. Concentrations as low as 0.5 microg/mL of PS-1 exhibited antileishmanial activity comparable to that of antimoniate of N-metilglucamine, while the antiplasmodial effect of PS-1 was evident at the concentration of 16 microg/mL, and reached an activity comparable to that of artesunate, at the concentration of 64 microg/mL. The high antiparasitic activity of PS-1, together with the unrelatedness of its chemical structure to any present antimicrobial drug, which prevents the development of cross-resistance, together with its non-toxicity to mammalian cells make this peptide a promising candidate for the treatment of malaria and leishmaniasis.

Biological investigation of a citrate-coated cobalt-ferrite-based magnetic fluid

The present study reports on several in vivo biological tests carried out with a cobalt–ferrite, citrate-coated, magnetic fluid sample developed for biomedical purposes. Systematic biological investigation was performed after endovenous injection in mice. Morphological analysis showed magnetic nanoparticle (MNP) infiltration in the parenchyma or vessels of all investigated organs. Nevertheless, at the investigated dose and period of treatment, no cell damage or inflammatory processes were observed. Cytometry alterations and genotoxic effects were not observed. Although precipitation of MNPs in tissues may be taken as undesirable, the absence of morphological alterations is very promising. The data show that the investigated sample is biocompatible and useful for biomedical applications.

Development and Antibacterial Activity of Cashew Gum-Based Silver Nanoparticles

The present study describes the development of a green synthesis of silver nanoparticles reduced and stabilized by exuded gum from Anacardium occidentale L. and evaluates in vitro their antibacterial and cytotoxic activities. Characterization of cashew gum-based silver nanoparticles (AgNPs) was carried out based on UV–Vis spectroscopy, transmission electron microscopy and dynamic light scattering analysis which revealed that the synthesized silver nanoparticles were spherical in shape, measuring about 4 nm in size with a uniform dispersal. AgNPs presented antibacterial activity, especially against Gram-negative bacteria, in concentrations where no significant cytotoxicity was observed.

Magnetic resonance and light microscopy investigation of a dextran coated magnetic fluid

A dextran-coated magnetite-based magnetic fluid (MF) sample (DexMF) was developed for cancer diagnostic and therapeutic purposes. In order to perform biological studies DexMF samples were endovenously injected into female Swiss mice. Magnetic resonance (MR) spectra showed a broad line around g=2, typical of magnetic nanoparticles (MNPs) suspended in a nonmagnetic matrix. The MR data showed that MNPs essentially spread in liver, spleen, and bone marrow. MNPs in blood stream were found up to 60 min after injection. Histological analysis also showed MNP agglomeration in liver, spleen, and bone marrow, from 1 h up to 28 days. No damaged cells or any other kind of alteration were observed in the investigated tissues. The data suggested that DexMF sample is biocompatible and adequate for biomedical applications.

Anthelmintic Activity In Vivo of Epiisopiloturine against Juvenile and Adult Worms of Schistosoma mansoni

Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported.

Collagen-based silver nanoparticles for biological applications: synthesis and characterization

BackgroundType I collagen is an abundant natural polymer with several applications in medicine as matrix to regenerate tissues. Silver nanoparticles is an important nanotechnology material with many utilities in some areas such as medicine, biology and chemistry. The present study focused on the synthesis of silver nanoparticles (AgNPs) stabilized with type I collagen (AgNPcol) to build a nanomaterial with biological utility. Three formulations of AgNPcol were physicochemical characterized, antibacterial activity in vitro and cell viability assays were analyzed. AgNPcol was characterized by means of the following: ultraviolet-visible spectroscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy, atomic absorption analysis, transmission electron microscopy and of X-ray diffraction analysis.ResultsAll AgNPcol showed spherical and positive zeta potential. The AgNPcol at a molar ratio of 1:6 showed better characteristics, smaller hydrodynamic diameter (64.34±16.05) and polydispersity index (0.40±0.05), and higher absorbance and silver reduction efficiency (0.645 mM), when compared with the particles prepared in other mixing ratios. Furthermore, these particles showed antimicrobial activity against both Staphylococcus aureus and Escherichia coli and no toxicity to the cells at the examined concentrations.ConclusionsThe resulted particles exhibited favorable characteristics, including the spherical shape, diameter between 64.34 nm and 81.76 nm, positive zeta potential, antibacterial activity, and non-toxicity to the tested cells (OSCC).

Influence of long-term treatment with pravastatin on the survival, evolution of cutaneous lesion and weight of animals infected by Leishmania amazonensis

The high toxicity of current drugs for treatment of leishmaniasis is a major hindrance for controlling the disease. Pravastatin is a well-known drug with anti-inflammatory and immunomodulatory properties that may modulate host defense mechanisms against Leishmania. We evaluated the influence of prolonged pravastatin treatment on the survival of Leishmania amazonensis-infected animals (BALB/c, C57BL6 mice and Syrian hamsters), including weekly measurement of cutaneous lesions (footpad thickness) and weight. Pravastatin improved survival of Leishmania-infected BALB/c mice but not of infected C57BL6 mice or hamsters. On the 50th week of follow-up, 71% of pravastatin-treated Leishmania-infected BALB/c mice were alive against 29% of control group (p<0.01). Low footpad thickness was found on BALB/c pravastatin treated mice from the 14th week (p<0.05), and 20th week onward for C57BL6 treated mice. Pravastatin treatment decreased weight loss in Leishmania-infected C57BL6 mice and Syrian hamsters, but not infected BALB/c mice. Our results points to beneficial effects of pravastatin on the evolution of the disease in the murine leishmaniasis model.

Morphometry of latent palmprints as a function of time

In many crimes, the elapsed time between production and collecting fingermark traces is crucial. and a method able to detect the aging of latent prints would represent an improvement in forensic procedures. Considering that as the latent print gets older, substantial changes in the relative proportion of individual components secreted by skin glands could affect the morphology of ridges, morphometry could be a potential tool to assess the aging of latent fingermarks. Then, considering the very limited research in the field, the present work aims to evaluate the morphometry of latent palmprint ridges, as a function of time, in order to identify an aging pattern. The latent marks were deposited by 20 donors on glass microscope slides considering pressure and contact angle, and then were maintained under controlled environmental conditions. The morphometric study was conducted on marks developed with magnetic powder in 7 different time intervals after deposition (0, 5, 10, 15, 20, 25 or 30 days); 60 ridges were evaluated for each developed mark. The results showed that: 1) the method for the replacement and mixing of skin secretions on the palm was appropriate to ensure reproducibility of latent prints, and 2) considering the studied group, there was a time-dependent reduction in the width of ridges and on the percentage of visible ridges over 30 days. Results suggest the possibility of using the morphometric method to determine an aging profile of latent palmprints on glass surface, aiming for forensic purposes.

The Skin Secretion of the Amphibian Phyllomedusa nordestina: A Source of Antimicrobial and Antiprotozoal Peptides

Antimicrobial peptides (AMPs) from the dermaseptin and phylloseptin families were isolated from the skin secretion of Phyllomedusa nordestina, a recently described amphibian species from Northeastern Brazil. One dermaseptin and three phylloseptins were chosen for solid phase peptide synthesis. The antiprotozoal and antimicrobial activities of the synthetic peptides were determined, as well as their cytotoxicity in mouse peritoneal cells. AMPs are being considered as frameworks for the development of novel drugs inspired by their mechanism of action.

Pravastatin modulates macrophage functions of Leishmania (L.) amazonensis-infected BALB/c mice

The control of leishmaniases poses an important challenge due to the scarcity and toxicity of the pharmacological options available. We have previously shown that pravastatin significantly improves the course of the disease in Leishmania (L.) amazonensis-infected BALB/c mice. Since the drug caused no direct effect on the parasite, we decided to evaluate its immunomodulatory action in this experimental model. To evaluate the impact of pravastatin treatment, BALB/c mice infected or not with L. (L.) amazonensis were treated with pravastatin (20 mg/kg daily) or saline during 30 or 90 days and phagocytosis, hydrogen peroxide, nitric oxide and the tumor necrosis factor production by peritoneal macrophages were assessed. We showed that pravastatin increased the phagocytosis mediated by complement and immunoglobulin receptors (63.5 to 130.3; p=0.03, t test), but not that occurring via pattern recognition receptors, induced a rise of nitric oxide production by macrophages (2.1 μM to 12.9 μM; p=0.04, Mann-Whitney test), endowing these cells to better kill ingested leishmania organisms, caused no modification of the otherwise increased production of hydrogen peroxide by macrophages, and reduced the overproduction of tumor necrosis factor (166.6 pg/mL to 3.9 pg/mL; p=0.016, Mann-Whitney test), a major component of the exacerbated inflammation associated to leishmaniases. Our findings point to the potential usefulness of pravastatin as an adjunct to the treatment of leishmaniases, based on its powerful immunomodulatory effects and low toxicity.