Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Efeito anti-inflamatório do heparinóide isolado do camarão Litopenaeus vannamei sobre a peritonite aguda

In recent years the heparin has been the subject of several studies that aim to expand its use as a therapeutic agent, due to its ability to modulate the activity of various proteins that play important roles in the regulation of pathophysiological processes. In several experiments and preclinical trials, heparin has demonstrated an anti-inflammatory role. However, its clinical use is limited, due to its strong anticoagulant activity and hemorrhagic complications. For this reason, considerable efforts have been employed in discovery of heparin analogous (heparinoid) with reduced side effects, that retain the anti-inflammatory properties of heparin. In this context, a heparinoid obtained from the head of Litopenaeus vannamei shrimp, which presents a structural similarity to heparin, showed, in previous studies, anti-inflammatory activity in a model of acute peritonitis with reduced anticoagulant effect in vitro and low hemorrhagic activity. Thus, the present work had as objective to evaluate the effect the heparinoid of the cephalothorax of gray shrimp on the acute inflammatory response in different times (3 or 6 hours after the induction of inflammatory stimulus), using the model of acute peritonitis induced in mice. It was also analyzed the HL effect over the activity of elastase, an enzyme involved in leukocyte recruitment. Furthermore to check if the different doses of heparin and heparinoid change the hemostatic balance in vivo, was assessed the effect of these compounds on the plasma clotting time in animals submitted to inflammation. The results show that in 3 hours, all doses of heparinoid were able to prevent efficiently in the acute inflammatory process without any anticoagulant effects, unlike the extrapolation dose of heparin, which has induced a large hemorrhage due its high anticoagulant activity. However, 6 hours after induction of inflammation, only the dosages of 0.1 and 1.0 μg/Kg of heparin and 1.0 μg/Kg of heparinoid kept anti-migratory effect, without changing of the hemostatic balance. These results indicate that the anti-migratory effect of theses compounds depends on the dosage and time of inflammatory stimulus. The HL and heparin were also able to inhibit the activity of the enzyme elastase. The discovery of this bioactive compound in the cephalothorax of shrimps can arouse great interest in biotechnology, since this compound could be useful as a structural model interesting for the development of new therapeutic agents for peritonitis

Estrutura genética de Chromis multilineata (Guichenot, 1853) (Perciformes Pomacentridae) na costa NE do Brasil e ilhas oceânicas: evidências de um passado evolutivo instável.

The fauna of Brazilian reef fishes comprises approximately 320 species distributed along the coast of the mainland and islands ocean. Little is known about the levels of connectivity between their populations, but has been given the interest in the relations between the offshore and the islands of the Brazil, in a biogeographical perspective. The oceanic islands Brazilian hosting a considerable number of endemic species, which are locally abundant, and divide a substantial portion of its reef fish fauna with the Western Atlantic. Among the richest families of reef fish in species are Pomacentridae. This study analyzed through analysis of sequences of the mitochondrial DNA control region (D-loop), the standards-breeding population of C. Multilineata in different areas of the NE coast of Brazil, involving both oceanic islands (Fernando de Noronha Archipelago and of St. Peter and St. Paul) and continental shelf (RN and BA). To this aim, partial sequences were used in the region HVR1 of mtDNA (312pb). The population structure and parameters for the estimates of genetic variability, molecular variance (AMOVA), estimation of the index for fixing (FST) and number of migrants were determined. The phylogenetic relationships between the populations were estimated using neighbor-joining (NJ) method. A group of Bayesian analysis was used to verify population structure, according to haplotype frequency of each individual. The genetic variability of populations was extremely high. The populations sampled show moderate genetic structure, with a higher degree of genetic divergence being observed for the sample of the Archipelago of St. Peter and St. Paul. At smaller geographical scale, the sample of Rio Grande do Norte and the Archipelago of Fernando de Noronha do not have genetic differentiation. Three moderately differentiated population groups were identified: a population group (I), formed by the Rio Grande do Norte (I') and the archipelago of Fernando de Noronha (I''), and two other different groups formed by the island population of the archipelago of Saint Peter and St. Paul (II) and Bahia (III). The genetic patterns found suggest that the species has suffered a relatively recent radiation favoring the absence of shared haplotypes. C. multilineata seems to constitute a relatively homogenous population along the West Atlantic coast, with evidence of a moderate population genetic structure in relation to the Archipelago of St. Peter and St. Paul. These data supports the importance of the dispersal larvae by marine current and the interpopulation similarity this species.