Azadirachta indica A. Juss. In Vivo Toxicity-An Updated Review.

The Neem tree, Azadirachta indica A. Juss., is known for its large spectrum of compounds with biological and pharmacological interest. These include, among others, activities that are anticancer, antibacterial, antiviral, and anti-inflammatory. Some neem compounds are also used as insecticides, herbicides, and/or antifeedants. The safety of these compounds is not always taken into consideration and few in vivo toxicity studies have been performed. The current study is a literature review of the latest in vivo toxicity of A. indica. It is divided in two major sections-aquatic animals toxicity and mammalian toxicity-each related to neem's application as a pesticide or a potential new therapeutic drug, respectively.

Biological Activities of Gedunin-A Limonoid from the Meliaceae Family.

Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.

Analysis of the microcrystalline inclusion compounds of triclosan with ß-cyclodextrin and its tris-O-methylated derivative.

Solid 1:1 inclusion compounds of triclosan with native and permethylated ß-cyclodextrin (ß-CD and TRIMEB) were prepared by co-crystallisation and co-evaporation, respectively, and studied by FT-IR and (13)C{(1)H} CP/MAS NMR spectroscopies, thermogravimetric analysis, X-ray diffraction and theoretical calculations. Results showed that triclosan inclusion into TRIMEB afforded an amorphous solid, whilst ß-CD·triclosan is composed of microcrystals belonging to two different phases. In the phase featuring larger crystals, X-ray diffraction was carried out and the ß-CD host units, packing head-to-head in infinite channels, were refined; the geometry for the included but highly disordered triclosan molecules was assessed by theoretical calculations. The bacterial growth inhibitory action of the inclusion compounds was studied in comparison to that of pure triclosan on Gram-negative (Salmonella, Escherichia) and Gram-positive strains (Bacillus, Listeria, Enterococcus and Staphylococcus) typically associated with human pathologies, and also on environmental bacteria isolated from different soil and water sources. The antimicrobial activities obtained in the present work showed that, of the two CD hosts, TRIMEB brings the most favourable carrier effect: it reduced the toxicity of triclosan against some of the environmental strains and afforded slightly higher action against virulent strains.

High-level vancomycin resistant Enterococcus faecium related to humans and pigs found in dust from pig breeding facilities.

Environmental dust from animal breeding facilities was never screened for the presence of enterococci, nor of vancomycin-resistant enterococci (VRE), despite the possibility of being a vehicle of transmission of strains and antibiotic resistance genes between food-producing animals and man. Bio-security measures in pig facilities include disinfection with biocides to avoid the dissemination of opportunistic pathogenic bacteria, namely enterococci and in particular VRE. We thus undertook collection of enterococci and VRE in a representative number of breeding pig facilities in Portugal (n=171) and analyzed their susceptibility to benzalkonium chloride (BC) and chlorhexidine (CHX). A prevalence of 15% of VRE was found, with 6% high-level resistance found, and MIC values for CHX and BC were similar to those commonly found among enterococcal isolates from related environments, 8 µg/ml and 4 µg/ml, respectively. Among the isolated high-level vancomycin resistant Enterococcus faecium carrying the vanA genotype, we found multilocus sequence types closely related to pig and human isolates from European countries and Brazil. These results strongly advise constant surveillance of this environment and its inclusion in future epidemiologic studies on VRE.

Involvement, and dissemination, of the enterococcal small multidrug resistance transporter QacZ in resistance to quaternary ammonium compounds.

OBJECTIVES: To investigate the role of a putative small multidrug resistance transporter, annotated in Enterococcus faecalis V583 genome as EFA0010 (we will refer to this gene as qacZ), in decreased susceptibility to biocides. METHODS: A derivative strain of V583, susceptible to erythromycin (V583ErmS), was complemented with pORI23 carrying the qacZ gene (strain EF-SAVE1). MICs of benzalkonium chloride, chlorhexidine and ethidium bromide were determined for the complemented strain and wild-type. RT-PCR and ethidium bromide efflux assays were performed in order to fully understand the role and specificity of the qacZ gene. The presence of qacZ in 73 enterococcal strains from different origins was investigated by PCR, and MICs of benzalkonium chloride and chlorhexidine were determined for the same strains. RESULTS: The complemented strain, EF-SAVE1, presented a higher MIC of benzalkonium chloride (8 mg/L) than V583ErmS (4 mg/L); the MICs of chlorhexidine and ethidium bromide were the same for both strains, 4 mg/L and 16 mg/L, respectively. Expression of qacZ was found to be higher in EF-SAVE1 and constitutive, i.e. not inducible by any of the three tested biocides. Overexpression of qacZ was not responsible for changes in ethidium bromide efflux. This gene was present in 52% of the enterococcal isolates studied and the MICs of benzalkonium chloride and chlorhexidine ranged between 2 and 8 mg/L. CONCLUSIONS: We demonstrate the involvement of the qacZ gene in tolerance to the quaternary ammonium compound benzalkonium chloride, but not ethidium bromide. This work constitutes the first report of a biocide resistance mechanism in E. faecalis, and reveals its dissemination amongst the genus Enterococcus.

Cyclodextrins improve the antimicrobial activity of the chloride salt of Ruthenium(II) chloro-phenanthroline-trithiacyclononane.

The complex [Ru([9]aneS(3))phenCl]Cl (phen = 1,10-phenanthroline) and its synthetic precursor [Ru([9]aneS(3))dmsoCl(2)] were immobilized in permethylated beta-cyclodextrin (TRIMEB). A new crystalline structure of the precursor, obtained from a batch ethanol solution at low temperature (4 degrees C), is fully described from single-crystal X-ray diffraction data. [Ru([9]aneS(3))phenCl]Cl was also encapsulated in native beta-cyclodextrin for comparison with the TRIMEB compound. All three compounds were obtained with a 1:1 host:guest stoichiometry and were studied by powder X-ray diffraction (including synchrotron radiation data), thermogravimetric analysis (TGA), (13)C{(1)H} CP/MAS NMR and FTIR spectroscopies. The bacterial growth inhibitory action of the complex [Ru([9]aneS(3))phenCl]Cl and its two cyclodextrin compounds was tested on Gram-negative (Salmonella, Escherichia) and Gram-positive strains (Bacillus, Listeria, Enterococcus and Staphilococcus) and results show a positive effect of cyclodextrin immobilization on the antimicrobial properties.