Melampolides from Argentinean Acanthospermum australe

The investigation of the ethanol extract of Acanthospermum australe, collected in the province of Misiones, Argentina, yielded eight melampolides (1–8) of the acanthospermal type. Two of them, 8β-hydroxy-9α-(2-methylbutyryloxy)-14-oxo-acanthospermolide (3) and 9α-hydroxy-8β-(2-methylbutyryloxy)-14-oxo-acanthospermolide (7) are new compounds. Two other compounds (4 and 8) have been previously reported, and the NMR data of 4 are corrected. Compounds 1, 2, 5 and 6 have not been previously reported, but are probably artifacts formed during extraction. Compounds 3, 6 and 7 showed slight antibiotic activity against Gram-positive bacteria.     

Detection and structural investigation of metabolites of stanozolol in human urine by liquid chromatography tandem mass spectrometry

The applicability of LC–MS/MS in precursor ion scan mode for the detection of urinary stanozolol metabolites has been studied. The product ion at m/z 81 has been selected as specific for stanozolol metabolites without a modification in A- or N-rings and the product ions at m/z 97 and 145 for the metabolites hydroxylated in the N-ring and 4-hydroxy-stanozolol metabolites, respectively. Under these conditions, the parent drug and up to 15 metabolites were found in a positive doping test sample. The study of a sample from a chimeric uPA-SCID mouse collected after the administration of stanozolol revealed the presence of 4 additional metabolites. The information obtained from the product ion spectra was used to develop a SRM method for the detection of 19 compounds. This SRM method was applied to several doping positive samples. All the metabolites were detected in both the uPA-SCID mouse sample and positive human samples and were not detected in none of the blank samples tested; confirming the metabolic nature of all the detected compounds. In addition, the application of the SRM method to a single human excretion study revealed that one of the metabolites (4ξ,16ξ-dihydroxy-stanozolol) could be detected in negative ionization mode for a longer period than those commonly used in the screening for stanozolol misuse (3′-hydroxy-stanozolol, 16β-hydroxy-stanozolol and 4β-hydroxy-stanozolol) in doping analysis. The application of the developed approach to several positive doping samples confirmed the usefulness of this metabolite for the screening of stanozolol misuse. Finally, a tentative structure for each detected metabolite has been proposed based on the product ion spectra measured with accurate masses using UPLC–QTOF MS.     

Antimicrobial Efficacy of Two Surface Barrier Discharges with Air Plasma against In Vitro Biofilms

The treatment of infected wounds is one possible therapeutic aspect of plasma medicine. Chronic wounds are often associated with microbial biofilms which limit the efficacy of antiseptics. The present study investigates two different surface barrier discharges with air plasma to compare their efficacy against microbial biofilms with chlorhexidine digluconate solution (CHX) as representative of an important antibiofilm antiseptic. Pseudomonas aeruginosa SG81 and Staphylococcus epidermidis RP62A were cultivated on polycarbonate discs. The biofilms were treated for 30, 60, 150, 300 or 600 s with plasma or for 600 s with 0.1% CHX, respectively. After treatment, biofilms were dispensed by ultrasound and the antimicrobial effects were determined as difference in the number of the colony forming units by microbial culture. A high antimicrobial efficacy on biofilms of both plasma sources in comparison to CHX treatment was shown. The efficacy differs between the used strains and plasma sources. For illustration, the biofilms were examined under a scanning electron microscope before and after treatment. Additionally, cytotoxicity was determined by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay with L929 mouse fibroblast cell line. The cell toxicity of the used plasma limits its applicability on human tissue to maximally 150 s. The emitted UV irradiance was measured to estimate whether UV could limit the application on human tissue at the given parameters. It was found that the UV emission is negligibly low. In conclusion, the results support the assumption that air plasma could be an option for therapy of chronic wounds.     

Influenza vaccine scarcity 2004-05: implications for biosecurity and public health preparedness

In the event of a bioterrorist event or a pandemic flu outbreak, it might be necessary to ration vaccine or other treatments. In this article, researchers examine how medical and public health decision makers negotiated the unanticipated 2004-05 influenza vaccine shortage, using the regional hospital system headquartered in Pittsburgh, Pennsylvania, as the focal study site. This account of that case study describes the circumstances that contributed to the national and local vaccine shortage; the improvisation by health policymakers, hospital administrators, physicians, and nurses to prevent influenza cases despite the shortfall; and some of the legal, fiscal, logistical, social, and political pressures that local health professionals faced in deciding who should receive the limited supply of influenza vaccine. This instance of an acute vaccine shortage provided an opportunity to examine the practical and ethical dilemmas of managing medical resources during a public health emergency.     

Population structure of nuclear and mitochondrial DNA variation among South American Burmeister’s porpoises (<Emphasis Type="Italic">Phocoena spinipinnis</Emphasis>)

Little is known about the biology of Burmeister’s porpoises (Phocoena spinipinnis), a small cetacean species endemic to South American waters. Information on stock structure, however, is urgently needed, as the species suffers from considerable mortality due to local fishery activities throughout its distribution range. Using mitochondrial control region sequences and 11 species-specific microsatellite loci, we assessed the genetic differentiation among 118 stranded, incidentally or directly-caught Burmeister’s porpoises from different localities in Peruvian, Chilean, and Argentine waters. F-statistics and Bayesian clustering analyses indicate a major population differentiation along the South American Pacific coast, separating Peruvian from both Chilean and Argentine individuals. Interestingly, this population boundary is consistent with the population structure found in another sympatrically-occurring cetacean species: the dusky dolphin (Lagenorhynchus obscurus). Given that vulnerability to local depletion for South American coastal porpoises and dolphins is probably highest in the Peruvian population (due to high exploitation levels and recurrent El Niño events), the genetic data reported here considerably strengthen the need for conservation efforts focused on regulation of catches in local waters. Moreover, we discuss possible genetic differentiation among Burmeister’s porpoises (i) from the Atlantic and Pacific Ocean and (ii) from different Peruvian harbors. Finally, cross-species amplifications suggest that our newly-developed microsatellite markers will be useful in population genetic studies in the five other extant porpoise species.     

A social component in the negative effect of sons on maternal longevity in pre-industrial humans

Due to their effect on maternal testosterone levels, sons are said to have reduced maternal longevity in pre-industrial humans. This analysis, using information from a Flemish agricultural village in the 18th-20th centuries, confirms the presence of a negative effect of sons on maternal longevity. However, the effect is mainly observed for mothers belonging to the least privileged social group and for sons surviving their fifth birthday. Both findings make the above-mentioned biological explanation relative. However, a plausible alternative, social interpretation is male-dominated intra-household resource competition. It is reasonable to assume that only sons above a certain age are able to claim a serious amount of resources and that competition is strongest within the least privileged social group.     

Landmarks help guide attention during visual search

Using a novel visual search paradigm McCarley et al. (2003) concluded that the oculomotor system keeps a history of 3-4 previously attended objects. However, their displays were visually sparse, denying participants structural information which might be used during normal search. This might have underestimated memory capacity. To examine this possibility, we included landmarks in the same search paradigm. Previously examined items were re-examined less frequently when landmarks were present compared to when they were absent. Results indicate that objects in the environment that share no features with search items are used as external support to aid memory in guiding visual search.     

The Drosophila MBD2/3 protein mediates interactions between the MI-2 chromatin complex and CpT/A-methylated DNA

Methyl-DNA binding proteins play an important role in epigenetic gene regulation. The Drosophila genome encodes a single protein (MBD2/3) with extended homologies to the vertebrate methyl-DNA binding proteins MBD2 and MBD3. However, very little is known about its functional properties. We have now characterized an MBD2/3 null mutant allele that is viable and fertile. This mutation caused a strong dominant suppression of position-effect variegation and also resulted in a high rate of chromosome segregation defects during early embryogenesis. Confocal analysis of mutant embryos showed local displacement of MI-2 from DNA and indicated that MBD2/3 is associated with only a subset of MI-2 complexes. In addition, band shift experiments demonstrated a specific binding of MBD2/3 to CpT/A-methylated DNA, which reflects the endogenous DNA methylation pattern of Drosophila. Consistently, the localization of MBD2/3 was disrupted in embryos with reduced levels of DNA methylation. Our data provide novel insights into the function of MBD2/3 proteins and strongly suggest the existence of methylation-dependent chromatin structures in Drosophila.