Ultrasound-assisted synthesis of functionalized 1,3-enynes by palladium-catalyzed cross-coupling reaction of alpha-styrylbutyltelluride with alkynyltrifluoroborate salts

An ultrasound-assisted synthesis of functionalized 1,3-enyne scaffolds is described and illustrated by palladium-catalyzed cross-coupling of potassium alkynyltrifluoroborate salts and alpha-styrylbutyltellurides. This procedure offers easy access to 1,3-enyne architecture that contains aliphatic and aromatic groups in good to excellent yields.

Bioequivalence study of two oral formulations of cefadroxil in healthy volunteers

Two different cefadroxil (CAS 50370-12-2) formulations were evaluated for their relative bioavailability in 24 healthy volunteers who received a single 500 mg oral dose of each preparation. An open, randomized clinical trial designed as a two-period crossover study with a 7-day washout period between doses was employed. Plasma samples for assessments of their cefadroxil concentration by HPLC-UV were obtained over 8 h after administration. Values of 48.94 +/- 10.18 mu g . h/ml for test, and 48.51 +/- 9.02 mu g . h/ml for the reference preparation AUC(0-t) demonstrate a nearly identical extend of drug absorption. Maximum plasma concentration C-max of 16.04 +/- 4.94 mu g/ml and 16.01 +/- 4.02 mu g/ml achieved for the test and reference preparations did not differ significantly. The parametric 90% confidence intervals (CI) of the mean of the difference (test-reference) between log-transformed values of the two formulations were 96.80% to 104.51% and 92.01% to 107.00% for AUC(0-t) and C-max, respectively. Since for both AUC(0-t) or C-max the 90% CI values are within the interval proposed by the Food and Drug Administration, the test product is bioequivalent to the reference product for both the rate and extent of absorption after single dose administration.

OCCURRENCE AND ANTIBIOTIC SENSIBILITY PROFILE OF Salmonella spp. ISOLATED FROM PORK MEAT CUTS COMMERCIALIZED IN THE OPEN MARKETS IN PELOTAS, RS (BRAZIL)

The objective of the present study was to evaluate the occurrence of Salmonella spp. in 15 samples of pork meat cuts (T-bone, shank, sausage and ribs) commercialized in open markets of Pelotas (RS, Brazil) and verify the prevalent serovars, and test the isolates profile of sensitivity to several antibiotics of importance in medicine (nalidixic acid, ampicillin, aztreonam, kanamycin, carbenicillin, cephalothin, cefoxitin, ceftriaxone, ciprofloxacin, chloramphenicol, gentamicin, sulfonamide, tetracycline and trimetoprina). Twelve samples (80%) were contaminated by Salmonella enterica, serovars Infantis, Derby, Panama and Typhimurium. All isolates were susceptible to trimetoprin, aztreonam, ciprofloxacin, ceftriaxone and cefoxitin. For the other antibiotics, the pattern of sensitivity varied as serovar. In addition, 39.1% of isolates showed up to be multiresistant.

Antimicrobial ent-pimarane diterpenes from Viguiera arenaria against Gram-positive bacteria

The dichloromethane crude extract from the roots of Viguiera arenaria (VaDRE) has been employed in an antimicrobial screening against several bacteria responsible for human pathologies. The main diterpenes isolated from this extract, as well as two semi-synthetic pimarane derivatives, were also investigated for the pathogens that were significantly inhibited by the extract (MIC values lower than 100 mu g mL(-1)). The VaDRE extract was significantly active only against Gram-positive microorganisms. The compounds ent-pimara-8(14),15-dien-19-oic acid (PA): PA sodium salt; ent-8(14),15-pimaradien-3 beta-ol; ent-15-pimarene-8 beta,19-diol; and ent-8(14),15-pimaradien-3 beta-acetoxy displayed the highest antibacterial activities (MIC values lower than 10 mu g mL(-1) for most pathogens). In conclusion, our results suggest that pimaranes are an important class of natural products for further investigations in the search of new antibacterial agents. (c) 2009 Elsevier B.V. All rights reserved.

Antimicrobial activity of crude extratcs of Petiveria alliacea L.

Antimicrobial activity of crude extratcs of Petiveria alliacea L.. Petiveria alliacea L. (Phytolaccacea) is an herbaceous plant of great importance in traditional medicine. This species have been widely used in several applications such as antirheumatic, anticarcinogenic, anti-flu, antitussive, analgesic, insecticidal, acaricidal, as well as bactericide and fungicide. Currently, the pathogenic microorganisms are acquiring resistence against the traditional antibiotics, and the search for new herbal antimicrobial agents has been intensified. The objective of this study was to evaluate the antifungal and antibacterial activity of several leaf crude extracts of P. alliacea against several strains of bacterias and yeasts namely Bacilus subtilis, Pseudomonas aeruginosa, Escherichia coli, Streptococcus mutans, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Candida parapsilosis, Candida kefyr and Candida albicans, using microdilution method. Promising results were observed for the 70% v/v ethanolic extract which presented minimum inhibitory concentration (MIC) from 250 to 760 mu g/mL for yeast. For the bacteria strains tested the MIC ranged between 240 to 3960 mu g/mL, depending of the extractive solution tested.

Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial

Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by depletion of the indigenous lactobacilli. Antimicrobial therapy is often ineffective. We hypothesized that probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 might provide an adjunct to antimicrobial treatment and improve cure rates. Sixty-four Brazilian women diagnosed with BV were randomly assigned to receive a single dose of tinidazole (2 g) supplemented with either 2 placebo capsules or 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14 every morning for the following 4 weeks. At the end of treatment (day 28), the probiotic group had a significantly higher cure rate of BV (87.5%) than the placebo group (50.0%) (p = 0.001). In addition, according to the Gram-stain Nugent score, more women were assessed with ""normal`` vaginal microbiota in the probiotic group (75.0% vs. 34.4% in the placebo group; p = 0.011). This study shows that probiotic lactobacilli can provide benefits to women being treated with antibiotics for an infectious condition.

Nosocomial outbreak by imipenem-resistant metallo-beta-lactamase-producing Pseudomonas aeruginosa in an adult intensive care unit in a Brazilian teaching hospital

Objective: To describe an outbreak of imipenem-resistant metallo-beta-lactamase-producing Pseudomonas aeruginosa, enzyme type bla, by horizontal transmission in patients admitted to a mixed adult ICU. Methods: A case-control study was carried out, including 47 patients (cases) and 122 patients (control) admitted to the mixed ICU of a university hospital in Minas Gerais. Brazil from November 2003 to July 2005. The infection site, risk factors, mortality, antibiotic susceptibility, metallo-beta-lactamase (MBL) production, enzyme type, and clonal diversity were analyzed, Results: A temporal/spatial relationship was detected in most patients (94%), overall mortality was 55.3%, and pneumonia was the predominant infection (85%). The majority of isolates (95%) were resistant to imipenem and other antibiotics, except for polymyxin, and showed MBL production (76.7%). Only bla SPM-1 (33%) was identified in the 15 specimens analyzed. In addition, 4 clones were identified, with a predominance of clone A (61.5%) and B (23.1%). On multivariate analysis, advanced age, mechanical ventilation, tracheostomy, and previous imipenem use were significant risk factors for imipenem-resistant P. aeruginosa infection. Conclusions: Clonal dissemination of MBL-producing P. aeruginosa strains with a spatial/temporal relationship disclosed problems in the practice of hospital infection control, low adherence to hand hygiene, and empirical antibiotic use. (C) 2008 Elsevier Espana, S.L. All rights reserved.

In vitro cultivation of Wolbachia pipientis in an Aedes albopictus cell line

A continuous cell line, Aa23, was established from eggs of a strain of the Asian tiger mosquito, Aedes albopictus, naturally infected with the intracellular symbiont Wolbachia pipientis. The resulting cell line was shown to be persistently infected with the bacterial endosymbiont. Treatment with antibiotics cured the cells of the infection. In the course of establishing this cell line it was noticed that RFLPs in the PCR products of two Wolbachia genes from the parental mosquitoes were fixed in the infected cell line. This indicates that the mosquito host was naturally superinfected with different Wolbachia strains, whereas the infected cell line derived from these mosquitoes only contained one of the original Wolbachia strains. The development of anin vitroculture system for this fastidious microorganism should facilitate molecular analysis of the reproduction distorting phenotypes it induces in natural arthropod hosts.

Acid-mediated conversion of methylene-interrupted bisepoxides to tetrahydrofurans: A biomimetic transformation

The acid-mediated transformation of syn and anti methylene interrupted cis,cis and cis,trans bisepoxides to tetrahydrofurans is high yielding, and demonstrates both regioselectivity and stereoselectivity. Trans,trans methylene interrupted bisepoxides do not yield tetrahydrofurans under the same conditions.

High affinity binding of albicidin phytotoxins by the AlbA protein from Klebsiella oxytoca

Albicidins are a family of phytotoxins and antibiotics which play an important role in the pathogenesis of sugarcane leaf scald disease. The albA gene from Klebsiella oxytoca encodes a protein which inactivates albicidin by heat-reversible binding. Albicidin ligand binding to a recombinant AlbA protein, purified by means of a glutathione S-transferase gene fusion system, is an almost instant and saturable reaction. Kinetic and stoichiometric analysis of the binding reaction indicated the presence of a single high affinity binding site with a dissociation constant of 6.4 x 10(-8) M. The AlbA-albicidin complex is stable from 4 to 40 degrees C, from ph 5 to 9 and in high salt solutions. Treatment with protein denaturants released all bound albicidin. These properties indicate that AlbA may be a useful affinity matrix for selective purification of albicidin antibiotics. AlbA does not bind to p-nitrophenyl butyrate or alpha-naphthyl butyrate, the substrates of the albicidin detoxification enzyme AlbD from Pantoea dispersa. The potential exists to pyramid genes for different mechanisms in transgenic plants to protect plastid DNA replication from inhibition by albicidins.

The Australian mortality decline: all-cause mortality 1788-1990

This review describes the Australian decline in all-cause mortality, 1788-1990, and compares this with declines in Europe and North America. The period until the 1870s shows characteristic 'crisis mortality', attributable to epidemics of infectious disease. A decline in overall mortality is evident from 1880. A precipitous fall occurs in infant mortality from 1900, similar to that in European countries. Infant mortality continues downward during this century (except during the 1930s), with periods of accelerated decline during the 1940s (antibiotics) and early 1970s. Maternal mortality remains high until a precipitous fall in 1937 coinciding with the arrival of sulphonamide. Excess mortality due to the 1919 influenza epidemic is evident. Artefactual falls in mortality occur in 1930, and for men during the war of 1939-1945. Stagnation in overall mortality decline during the 1930s and 1945-1970 is evident for adult males, and during 1960-1970 for adult females. A decline in mortality is registered in both sexes from 1970, particularly in middle and older age groups, with narrowing of the sex differential. The mortality decline in Australia is broadly similar to those of the United Kingdom and several European countries, although an Australian advantage during last century and the first part of this century may have been due to less industrialisation, lower population density and better nutrition. Australia shows no war-related interruptions in the mortality decline. Australian mortality patterns from 1970 are also similar to those observed in North America and European countries (including the United Kingdom, but excluding Eastern Europe).

A novel two-chain proteinase inhibitor generated by circularization of a multidomain precursor protein

Female reproductive tissues of the ornamental tobacco amass high levels of serine proteinase inhibitors (PIs) for protection against pests and pathogens. These PIs are produced from a precursor protein composed of six repeats each with a protease reactive site. Here we show that proteolytic processing of the precursor generates five single-chain PIs and a remarkable two-chain inhibitor formed by disulfide-bond Linkage of Nand C-terminal peptide fragments. Surprisingly, PI precursors adopt this circular structure regardless of the number of inhibitor domains, suggesting this bracelet-like conformation is characteristic of the widespread potato inhibitor II (Pot II) protein family.

High level of aspartic acid-bond isomerization during the synthesis of an N-linked tau glycopeptide

An increased degree of utilization of the potential N-glycosylation site In the fourth repeat unit of the human tau protein may be involved in the inability of tau to bind to the corresponding tubulin sequence(s) and in the subsequent development of the paired helical filaments of Alzheimer's disease. To model these processes, we synthesized the octadecapeptide spanning this region without sugar, and with the addition of an N-acetyl-glucosamine moiety. The carbohydrate-protected, glycosylated asparagine was incorporated as a building block during conventional Fmoc-solid phase peptide synthesis. While the crude non-glycosylated analog was obtained as a single peptide, two peptides with, the identical, expected masses, in approximately equal amounts, were detected after the cleavage of the peracetylated glycopeptide. Surprisingly, the two glycopeptides switched positions on the reversed-phase high performance liquid chromatogram after removal of the sugar-protecting acetyl groups. Nuclear magnetic resonance spectroscopy and peptide sequencing identified the more hydrophobic deprotected peak as the target peptide, and the more hydrophilic deprotected peak as a peptide analog in which the aspartic acid-bond just preceding the glycosylated asparagine residue was isomerized resulting in the formation of a beta-peptide. The anomalous chromatographic behavior of the acetylated beta-isomer could be explained on the basis of the generation of an extended hydrophobic surface which is not present in any of the other three glycopeptide variants. Repetition of the syntheses, with altered conditions and reagents, revealed reproducibly high levels of aspartic acid-bond isomerization of the glycopeptide as well as lack of isomerization for the non-glycosylated parent analog. If similar increased aspartic acid-bond isomerization occurs in vivo, a protein modification well known to take place for both the amyloid deposits and the neurofibrillary tangles in Alzheimer's disease, this process may explain the aggregation of glycosylated tau into the paired helical filaments in the affected brains. Copyright (C) 1999 European Peptide Society and John Wiley & Sons, Ltd.

Chemical synthesis, antibacterial activity and conformation of diptericin, an 82-mer peptide originally isolated from insects

The small amounts of antibacterial peptides that can be isolated from insects do not allow detailed studies of their range of activity, side-chain sugar requirements, or their conformation, factors that frequently play roles in the mode of action. In this paper, we report the solid-phase step-by-step synthesis of diptericin, an 82-mer peptide, originally isolated from Phormia terranovae. The unglycosylated peptide was purified to homogeneity by conventional reversed-phase high performance liquid chromatography, and its activity spectrum was compared to that Of synthetic unglycosylated drosocin, which shares strong sequence homology with diptericin's N-terminal domain. Diptericin appeared to have antibacterial activity:for only a limited number of Gram-negative bacteria. Diptericin's submicromolar potency against Escherichia coli strains indicated that, in a manner similar to drosocin, the presence of the carbohydrate side chain is not,necessary to kill bacteria. Neither the N-terminal, drosocin-analog fragment, nor the C-terminal, glycine-rich attacin-analog region was active against any of the bacterial strains studied, regardless of whether the Gal-GalNAc disaccharide units were attached. This suggested that the active site of diptericin fell outside the drosocin or attacin homology domains. In addition, the conformation of diptericin did not seem to play a role in the antibacterial activity, as was demonstrated by the complete lack of ordered structure by two-dimensional nuclear magnetic resonance spectroscopy and circular dichroism. Diptericin completely killed bacteria within I h, considerably faster than drosocin and the attacins; unlike some other, fast-acting antibacterial peptides, diptericin did not lyse normal mammalian cells. Taken together, these data suggest diptericin does not belong to any known class of antibacterial peptides.