Histoplasmosis Outbreaks in Brazil: Lessons to Learn About Preventing Exposure

Mycopathologia - Histoplasmosis is considered the most common invasive opportunistic fungal disease in the Americas, with outbreaks and micro-epidemics reported for over 80 years. In...     

Antimicrobial activity and antibiotic synergy of a biphosphinic ruthenium complex against clinically relevant bacteria

Abstract

The aim of this study was to investigate the antibacterial activity, antibiotic-associated synergy, and anti-biofilm activity of the ruthenium complex, cis-[RuCl₂ (dppb) (bqdi)]²⁺ (RuNN). RuNN exhibited antimicrobial activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 15.6 to 62.5?µg ml^?1 and minimum bactericidal concentration (MBC) values ranging from 62.5 to 125?µg ml^?1. A synergistic effect against Staphylococcus spp. was observed when RuNN was combined with ampicillin, and the range of associated fractional inhibitory concentration index (FICI) values was 0.187 to 0.312. A time-kill curve indicated the bactericidal activity of RuNN in the first 1–5?h. In general, RuNN inhibited biofilm formation and disrupted mature biofilms. Furthermore, RuNN altered the cellular morphology of S. aureus biofilms. Further, RuNN did not cause hemolysis of erythrocytes. The results of this study provide evidence that RuNN is a novel therapeutic candidate to treat bacterial infections caused by Staphylococcus biofilms.     

Multi-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosis

Compound ITH33/IQM9.21 (ITH/IQM) belongs to a new family of l-glutamic acid derivatives with antioxidant and neuroprotective properties on in vitro and in vivo models of stroke. Because neuronal damage after brain ischemia is tightly linked to excess Ca²⁺ entry and neuronal Ca²⁺ overload, we have investigated whether compound ITH/IQM antagonises the elevations of the cytosolic Ca²⁺ concentrations ([Ca²⁺]_c) and the ensuing exocytotic responses triggered by depolarisation of bovine chromaffin cells. In fluo-4-loaded cell populations, ITH/IQM reduced the K⁺-evoked [Ca²⁺]_c transients with an IC₅₀ of 5.31 μM. At 10 μM, the compound decreased the amplitude and area of the Ca²⁺ transient elicited by challenging single fura-2-loaded cells with high K⁺, by 40% and 80%, respectively. This concentration also caused a blockade of K⁺-induced catecholamine release at the single-cell level (78%) and cell populations (55%). These effects are likely due to blockade of the whole-cell inward Ca²⁺ currents (IC₅₀ = 6.52 μM). At 10 μM, ITH/IQM also inhibited the Ca²⁺-dependent outward K⁺ current, leaving untouched the voltage-dependent component of I_K. The inward Na⁺ current was unaffected. Inhibition of depolarisation-elicited Ca²⁺ entry, [Ca²⁺]_c elevation and exocytosis could contribute to the neuroprotective effects of ITH/IQM in vulnerable neurons undergoing depolarisation during brain ischemia.     

Excess iron-induced changes in the photosynthetic characteristics of sweet potato

Iron (Fe) is an essential nutrient for plant growth and development. In plant tissues, approximately 80% of Fe is found in photosynthetic cells. This study was carried out to determine the effect of different iron concentrations on the photosynthetic characteristics of sweet potato plants. The fluorescence transient of chlorophyll a (OJIP), chlorophyll index and gas exchange were measured in plants grown for seven days in Hoagland solution containing an iron concentration of 0.45, 0.90, 4.50 or 9.00 mM Fe (as Fe-EDTA). The initial and maximum fluorescence increased in the plants receiving 9.00 mM Fe. In the analysis of the fluorescence kinetic difference, L- and K-bands appeared in all of the treatments, but the amplitude was higher in plants receiving 4.50 or 9.00 mM Fe. In plants grown in 9.00 mM Fe, the parameters of the JIP-Test indicated a better efficiency in the capture, absorption and use of light energy, and although the chlorophyll index was higher, the net photosynthesis was lower. The overall data showed that sweet potato plants subjected to high iron concentrations may not exhibit the toxicity symptoms, but the light reactions of photosynthesis can be affect, which may result in a declining net assimilation rate.     

Synthesis of potentially bioactive PABA-related <Emphasis Type="Italic">N</Emphasis>-(aminoalkyl)lactamic amino acids and esters via selective S<Subscript>N</Subscript>Ar reactions

Abstract  

Potentially bioactive N-(aminoalkyl)lactamic amino acids and esters were synthesized in satisfactory to good yields by S_NAr reactions of aromatic acids with N-(3-aminopropyl)lactams followed by esterification with tertiary amino alcohols. The addition–elimination S_NAr mechanism was confirmed by NMR and MS measurements.     

Evaluation of bacterial surfactant toxicity towards petroleum degrading microorganisms

The acute toxicity of bacterial surfactants LBBMA111A, LBBMA155, LBBMA168, LBBMA191 and LBBMA201 and the synthetic surfactant sodium dodecyl sulfate (SDS) on the bioluminescent bacterium Vibrio fischeri was evaluated by measuring the reduction of light emission (EC(20)) by this microorganism when exposed to different surfactant concentrations. Moreover, the toxic effects of different concentrations of biological and synthetic surfactants on the growth of pure cultures of isolates Acinetobacter baumannii LBBMA04, Acinetobacter junni LBBMA36, Pseudomonas sp. LBBMA101B and Acinetobacter baumanni LBBMAES11 were evaluated in mineral medium supplemented with glucose. The EC(20) values obtained confirmed that the biosurfactants have a significantly lower toxicity to V. fischeri than the SDS. After 30 min of exposure, bacterial luminescence was almost completely inhibited by SDS at a concentration of 4710 mg L(-1). Growth reduction of pure bacterial cultures caused by the addition of biosurfactants to the growth medium was lower than that caused by SDS.     

Development of 99mTc(CO)₃-dendrimer-FITC for cancer imaging

Study of fluorophore and technetium labeling of poly(amido)-amine (PAMAM) generation 4 (G4) dendrimer and its evaluation as potential molecular imaging agent in both normal and melanoma-bearing mice, are described. Dendrimers were first conjugated with FITC (fluorescein isothiocyanate). Dendrimer-FITC was then incubated with the intermediate [(99m)Tc(CO)(3)(H(2)O)(3)](+) and purified by gel filtration. Biodistribution and scintigraphy images were performed administrating (99m)Tc(CO)(3)-dendrimer-FITC to normal mice (NM) or melanoma-bearing mice (MBM). Cryostat tissue sections from MBM mice were analyzed by confocal microscopy. Radiolabeling yield of dendrimer was approx. 90%. The (99m)Tc(CO)(3)-dendrimer-FITC complex was stable for at least 24h. Biodistribution studies in NM showed blood clearance with hepatic and renal depuration. MBM showed a similar pattern of biodistribution with high tumor uptake that allowed tumor imaging. Confocal microscopy analysis showed cytoplasmic distribution of (99m)Tc(CO)(3)-dendrimer-FITC.     

Structural, functional, and bioinformatics studies reveal a new snake venom homologue phospholipase A₂ class

Phospholipases A₂ (PLA₂s) are enzymes responsible for membrane disruption through Ca²⁺‐dependent hydrolysis of phospholipids. Lys49‐PLA₂s are well‐characterized homologue PLA₂s that do not show catalytic activity but can exert a pronounced local myotoxic effect. These homologue PLA₂s were first believed to present residual catalytic activity but experiments with a recombinant toxin show they are incapable of catalysis. Herein, we present a new homologue Asp49‐PLA₂ (BthTX‐II) that is also able to exert muscle damage. This toxin was isolated in 1992 and characterized as presenting very low catalytic activity. Interestingly, this myotoxic homologue Asp49‐PLA₂ conserves all the residues responsible for Ca²⁺ coordination and of the catalytic network, features thought to be fundamental for PLA₂ enzymatic activity. Previous crystallographic studies of apo BthTX‐II suggested this toxin could be catalytically inactive since a distortion in the calcium binding loop was observed. In this article, we show BthTX‐II is not catalytic based on an in vitro cell viability assay and time‐lapse experiments on C2C12 myotube cell cultures, X‐ray crystallography and phylogenetic studies. Cell culture experiments show that BthTX‐II is devoid of catalytic activity, as already observed for Lys49‐PLA₂s. Crystallographic studies of the complex BthTX‐II/Ca²⁺ show that the distortion of the calcium binding loop is still present and impairs ion coordination even though Ca²⁺ are found interacting with other regions of the protein. Phylogenetic studies demonstrate that BthTX‐II is more phylogenetically related to Lys49‐PLA₂s than to other Asp49‐PLA₂s, thus allowing Crotalinae subfamily PLA₂s to be classified into two main branches: a catalytic and a myotoxic one. Proteins 2010. © 2010 Wiley‐Liss, Inc.