Monoamine oxidase inhibitory activities of indolylalkaloid toxins from the venom of the colonial spider Parawixia bistriata: Functional characterization of PwTX-I

Colonial spiders evolved a differential prey-capture behaviour in concert with their venom chemistry, which may be a source of novel drugs. Some highly active tetrahydro-beta-carboline (TH beta C) toxins were recently isolated from the venom of the colonial spider Parawixia bistriata; the spiders use these toxins as part of their chemical arsenal to kill and/or paralyze preys. The major TH beta C compound isolated from this venom was identified as 6-hydroxytrypargine, also known as PwTX-I. Most natural compounds of animal origin occur in low abundance, and the natural abundance of PwTX-I is insufficient for complete functional characterization. Thus, PwTx-I was synthesized using a Pictet-Spengler condensation strategy, and the stereoisomers of the synthetic toxin were separated by chiral chromatography. The fraction of venom containing a mixture of three natural TH beta C toxins and enantiomers of PwTx-I were analyzed for inhibition of monoamine oxidase (MAO)-A and -B and for toxicity to insects. We reveal that the mixture of the natural TH beta C toxins, as well as the enantiomers of PwTx-I, were non-competitive inhibitors of MAO-A and MAO-B and caused potent paralysis of honeybees. The (-)-PwTX-I enantiomer is 2-fold more potent than the (+)-PwTX-I enantiomer in the assays performed. (C) 2009 Elsevier Ltd. All rights reserved.

Crystal structure of Escherichia coli xanthine phosphoribosyltransferase

Xanthine phosphoribosyltransferase (XPRT; EC 2.4.2.22) from Escherichia coil is a tetrameric enzyme having 152 residues per subunit. XPRT catalyzes the transfer of the phosphoribosyl group from 5-phospho-alpha-D-ribosyl l-pyrophosphate (PRib-PP) to the 6-oxopurine bases guanine, xanthine, and hypoxanthine to form GMP, XMP, and IMP, respectively. Crystals grown in the absence of substrate or product were used to determine the structure of XPRT at a resolution of 1.8 Angstrom by multiple isomorphous replacement. The core structure of XPRT includes a five-stranded parallel B-sheet surrounded by three or-helices, which is similar to that observed in other known phosphoribosyltransferase (PRTase) structures. The XPRT structure also has several interesting features. A glutamine residue in the purine binding site may be responsible for the altered 6-oxopurine base specificity seen in this enzyme compared to other 6-oxopurine PRTases. Also, we observe both a magnesium ion and a sulfate ion bound at the PRib-PP binding site of XPRT. The sulfate ion interacts with Arg-37 which has a cis-peptide conformation, and the magnesium ion interacts with Asp-89, a highly conserved acidic residue in the PRib-PP binding site motif. The XPRT structure also incorporates a feature which has not been observed in other PRTase structures. The C-terminal 12 residues of XPRT adopt an unusual extended conformation and make interactions with a neighboring subunit. The very last residue, Arg-152, could form part of the active site of a symmetry-related subunit in the XPRT tetramer.

AIDS in Latin America: assessing the current status of the epidemic and the ongoing response

Background This article provides a summary of the current status of the HIV/AIDS epidemic in Latin America, as well as an outline of the diverse responses to it. Methods A search of international databases (Pubmed and ISI-Web of Science), regional databases (Scielo and Lilacs), regional and national documents and UNAIDS reports. Data are presented according to subregion. Results In Mexico HIV remains concentrated among urban men who have sex with men (MSM), and has been growing among injecting drug users (IDU) and in rural areas in relation to migration. An increasing proportion of women among those affected is observed in all countries in Central America, the most affected region, as well as increasing the impact on other vulnerable groups, such as indigenous populations. The Andean Countries have urban epidemics concentrated among MSM. In Peru, non-traditional vulnerable populations were identified. In the Southern Cone heterosexual transmission became more relevant, probably in connection with IDU epidemics and is increasingly affecting lower income groups. Incidence rates have been declining since 2002 in Brazil, the first country to guarantee free, universal access to antiretrovirals, where one-third of drug-nave patients are still initiating treatment at an advanced stage. Generally, access to treatment has improved as a result of support from the Global Fund and other initiatives, but there are concerns regarding coverage, equity and sustainability. Conclusions HIV is still concentrated among MSM in Latin America. Non-traditional vulnerable groups such as migrants and lower income populations, usually considered part of the general population, deserve attention. Programmes confronting sexual exclusion are still needed. Access to treatment has improved over time, but inequalities persist.

Prevalence of trachoma in a population of the upper Rio Negro Basin and risk factors for active disease

Purpose: To determine the prevalence of trachoma in Sao Gabriel da Cachoeira (SGC), the only urban community of the upper Rio Negro Basin of the Amazon state in Brazil, near the Colombian border, and to investigate the risk factors associated with the active forms of the disease. Methods: A total of 1702 people (440 children up to 9 years and 1069 adults aged 15 years and above) were examined. The sample was selected from a probabilistic household sampling procedure based on census data and a previous study of trachoma prevalence in Sao Gabriel da Cachoeira. A two-stage probabilistic household cluster sample was drawn. Household units were randomly selected within each cluster. A variety of socioeconomic and hygiene variables were studied in order to determine the risk factors for active trachoma in a household. Results: The total prevalence of trachoma was 8.9%. Prevalence of active trachoma (TF and/or TI) in children aged 1-9 years was 11.1% and trachomatous trichiasis in adults aged 15 years and above was 0.19%. Trachomatous scarring reached a peak of 22.4% for subjects between 50 to 60 years of age. Corneal opacity occurred in subjects aged 50 years and older with a prevalence of 2.0%. No sex effect was found on the overall prevalence of trachoma in SGC. Risk factors associated with active trachoma were mainly related to poor socioeconomic indicators. Conclusions: Despite the ubiquitous presence of water, the analysis of the risk factors associated with the active forms of the disease supports the idea that a low personal standard of hygiene and not water availability per se, is the key factor associated with trachoma.

Report from The International Society for Nomenclature of Paediatric and Congenital Heart Disease: cardiovascular catheterisation for congenital and paediatric cardiac disease (Part 1-Procedural nomenclature)

Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and on the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the first part of a two-part series. Part 1 will cover the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. This procedural nomenclature of The International Paediatric and Congenital Cardiac Code will be used in the IMPACT Registry (TM) (IMproving Pediatric and Adult Congenital Treatment) of the National Cardiovascular Data Registry (R) of The American College of Cardiology. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.

Report from The International Society for Nomenclature of Paediatric and Congenital Heart Disease: cardiovascular catheterisation for congenital and paediatric cardiac disease (Part 2-Nomenclature of complications associated with interventional cardiology)

Interventional cardiology for paediatric and congenital cardiac disease is a relatively young and rapidly evolving field. As the profession begins to establish multi-institutional databases, a universal system of nomenclature is necessary for the field of interventional cardiology for paediatric and congenital cardiac disease. The purpose of this paper is to present the results of the efforts of The International Society for Nomenclature of Paediatric and Congenital Heart Disease to establish a system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease, focusing both on procedural nomenclature and the nomenclature of complications associated with interventional cardiology. This system of nomenclature for cardiovascular catheterisation for congenital and paediatric cardiac disease is a component of The International Paediatric and Congenital Cardiac Code. This manuscript is the second part of the two-part series. Part 1 covered the procedural nomenclature associated with interventional cardiology as treatment for paediatric and congenital cardiac disease. Part 2 will cover the nomenclature of complications associated with interventional cardiology as treatment for paediatric and congenital cardiac disease.

Oral lesions and immune reconstitution syndrome in HIV+/AIDS patients receiving highly active antiretroviral therapy. Epidemiological evidence

Objective: To determine whether opportunistic oral infections associated to HIV infection (OOI-HIV) are found in HIV+/AIDS patients with immune reconstitution related to highly active antiretroviral therapy (HAART). Methods. From among 1100 HIV+/AIDS patients (Service of Internal Medicine, Carlos Haya Hospital, Malaga, Spain) subjected to review of the oral cavity between January 1996 and May 2007, we identified those examined in 1996 and which were again examined between 1997 and 2007, and were moreover receiving HAART. The following data were collected: age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4+ lymphocytes/ml, and viral load (from 1997 onwards). We identified those subjects with an increase in CD4+ lymphocytes/ ml associated to HAART, and classified them as subjects with quantitative evidence of immune reconstitution (QEIR). Among these individuals with QEIR we moreover identified those with undetectable viral loads (QEIR+VL), and differentiated those patients with an increase in CD4+ lymphocytes > 500/ml (QEIRm+VL). In each group we determined the prevalence of OOI-HIV, following the diagnostic recommendations of the EC-Clearinghouse (CDC-Atlanta, USA - WHO). In addition, we analyzed the prevalence of OOI-HIV in the different groups in relation to the duration of HAART. Results. A total of 86 subjects were included (44 females and 42 males; 19 heterosexuals, 34 male homosexuals, and 33 intravenous drug abusers). Forty-two patients showed QEIR: 21 belonged to the QEIR+VL group, and 17 conformed the QEIRm+VL group. The prevalence of OOI-HIV per group was as follows: QEIR = 54.8%; QEIR+VL = 33%; QEIRm+VL = 35%. The most prevalent lesion in all groups was erythematous candidiasis. OOI-HIV increased with the duration of HAART (p=0.008), and were seen to be dependent upon late appearance of the mycotic lesions ( after 24 months under HAART). Conclusions: It is suggested that opportunistic oral infections associated to HIV infection form part of the clinical picture of immune reconstitution inflammatory syndrome, though such infections are of late onset.

Closure of the Challinor Centre II: An extended report on 95 individuals after 12 months of community living

As part of an institutional closure programme, 95 individuals with an intellectual disability were relocated to community-based group homes. Each individual was assessed 6 months prior to the relocation and then again after 1, 6, and 12 months of community living. Assessments involved ratings of adaptive and maladaptive behaviour, choice-making, and life circumstances. The group means comparing institution to community ratings showed improvements in adaptive functioning but no significant change in maladaptive behaviour. There were also improvements in life circumstances and increased opportunities for choice-making following relocation to the community. These outcomes suggest that relocation to the community was associated with a more active and normalised lifestyle than experienced in the institutional setting.

Precipitation hardening of Cu-Fe-Cr alloys - Part I - Mechanical and electrical properties

This research is part of a project whose scope was to investigate the engineering properties of new non-commercial alloy formulations based on the Cu rich corner of the Cu-Fe-Cr ternary system with the primary aim of exploring the development of a new cost-effective high-strength, high-conductivity copper alloy. The literature indicated that Cu rich Cu-Cr and Cu-Fe alloys have been thoroughly investigated. A number of commercial alloys have been developed and these are used for a variety of applications requiring combinations of high-strength, high-conductivity and resistance to softening. Little evidence was found in the literature that the Cu rich corner of the Cu-Fe-Cr system had previously been investigated for the purpose of developing high-strength, high-conductivity copper alloys resistant to softening. The aim of these present investigations was to explore the possibility that new alloys could be developed that combined the properties of both sets of alloys, ie large precipitation hardening response combined with the ability to stabilise cold worked microstructures to high temperatures while at the same maintain high electrical conductivity. To assess the feasibility of this goal the following alloys were chosen for investigation: Cu-0.7wt%Cr-0.3wt%Fe, Cu-0.7wt%Cr-0.8wt%Fe, Cu-0.7wt%Cr-2.0wt%Fe. This paper reports on the mechanical property investigation which indicated that the Cu-0.7wt%Cr-0.3wt%Fe, and Cu-0.7wt%Cr-2.0wt%Fe alloys were worthy of further investigation. (C) 2001 Kluwer Academic Publishers.

Precipitation hardening of Cu-Fe-Cr alloys - Part II - Microstructural characterisation

This research is part of a project whose scope was to investigate the engineering properties of new non-commercial alloy formulations based on the Cu rich corner of the Cu-Fe-Cr ternary system with the primary aim of exploring the development of a new cost-effective high-strength, high-conductivity copper alloy. Promising properties have been measured for the following alloys: Cu-0.7wt%Cr-0.3wt%Fe and Cu-0.7wt%Cr-2.0wt%Fe. This paper reports on the microstructural characterisation of these alloys and discusses the mechanical and electrical properties of these alloys in terms of their microstructure, particularly the formation of precipitates. These alloys have evinced properties that warrant further investigation. Cost modelling has shown that Cu-0.7wt%Cr-0.3wt%Fe is approximately 25% cheaper to produce than commercial Cu-1%Cr. It has also been shown to be more cost efficient on a yield stress and % IACS per dollar basis. The reason for the cost saving is that the Cu-0.7%Cr-0.3%Fe alloy can be made with low carbon ferro-chrome additions as the source of chromium rather than the more expensive Cu-Cr master-alloy. For applications in which cost is one of the primary materials selection criteria, it is envisaged that there would be numerous applications in both cast and wrought form, where the Cu-0.7%Cr-0.3%Fe alloy would be more suitable than Cu-1%Cr. (C) 2001 Kluwer Academic Publishers.

Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors

Recombinant forms of the dengue 2 virus NS3 protease linked to a 40-residue co-factor, corresponding to part of NS2B, have been expressed in Escherichia coli and shown to be active against para-nitroanilide substrates comprising the P6-P1 residues of four substrate cleavage sequences. The enzyme is inactive alone or after the addition of a putative 13-residue co-factor peptide but is active when fused to the 40-residue co-factor, by either a cleavable or a noncleavable glycine linker. The NS4B/NS5 cleavage site was processed most readily, with optimal processing conditions being pH 9, I = 10 mm, 1 mm CHAPS, 20% glycerol. A longer 10-residue peptide corresponding to the NS2B/NS3 cleavage site (P6-P4') was a poorer substrate than the hexapeptide (P6-P1) para-nitroanilide substrate under these conditions, suggesting that the prime side substrate residues did not contribute significantly to protease binding. We also report the first inhibitors of a co-factor-complexed, catalytically active flavivirus NS3 protease. Aprotinin was the only standard serine protease inhibitor to be active, whereas a number of peptide substrate analogues were found to be competitive inhibitors at micromolar concentrations.