ß-Lactams: chemical structure, mode of action and mechanisms of resistance

This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This review also summarizes the main resistance mechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases and AmpC β-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump β-lactams out of the bacterial cell.

Antibiotic resistance in enterobacteriaceae isolated from Portuguese deli meats

This study aimed to identify the presence of β-lactam-resistant bacteria in different types of Portuguese deli meats. The numbers of ampicillin resistant bacteria varied from negative in 25 g to 1.0 × 108colony-forming units/g. Within 78 randomly selected β-lactam-resistant bacteria, 24 different resistant phenotypes were found and 35.9% were multidrug resistant (MDR). The majority (87.2%) of the isolates identified belonged to the Enterobacteriaceae family. The presence of the blaTEM gene was detected in 23 out of 67 isolates (34.3%) and 16 of them presented MDR phenotypes. Four Klebsiella oxytoca isolates (6%) harbored a gene for the CTX-M/OXY-type enzyme. The direct sequencing of their purified amplicons confirmed the presence of three types of blaOXYgenes (blaOXY-1, blaOXY-2 and blaOXY-5). These results suggest that without good hygienic practices, deli meats may act as a vehicle of transfer of β-lactam-resistant bacteria to the gastrointestinal tract of consumers.

Magnesium, insulin resistance and body composition in healthy postmenopausal women

Objective: This study was conducted to determine the association between magnesium (Mg), body composition and insulin resistance in 136 sedentary postmenopausal women, 50 to 77 years of age. Methods: Diabetics, hypertensives and women on hormonal replacement therapy were excluded and the remaining 74 were divided according to BMI≥25 (obese: OG) and BMI<25 kg/m2 (non-obese: NOG). Nutritional data disclosed that intakes were high for protein and saturated fat, low for carbohydrates, polyunsaturated fat and Mg and normal for the other nutrients, according to recommended dietary allowances (RDA). Mg values in red blood cells (RBC-Mg) and plasma (P-Mg), were determined, as were fasting glucose, and insulin levels, Homeostasis Model Assessment (HOMA), body mass index (BMI), body fat percent (BF %), abdominal fat (AF) and free fat mass (FFM). Results: RBC-Mg values were low in both groups when compared with normal values. There were significant differences in body composition parameters, HOMA and insulin levels, with higher basal insulin levels in OG. RBC-Mg was directly correlated with insulin, HOMA and FFM in both groups, according to Pearson correlations. HOMA in OG was also directly correlated with BMI, FFM and AF. In NOG, HOMA was only correlated with FFM. The low RBC-Mg levels observed were probably due to low Mg intake and to deregulation of factors that control Mg homeostasis during menopause. Conclusions: Both Mg deficit and obesity may independently lead to a higher risk for insulin resistance and cardiovascular disease.

Unlocking the technology-mediated learning process : insights and articulating actions for an institutional approach

This paper is part of the results from the project "Implementation Strategies and Development of an Open and Distance Education System for the University of the Azores" funded by the European Social Fund. http://hdl.handle.net/10400.3/2327

Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes’ upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2’-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients

β-Lactams: chemical structure, mode of action and mechanisms of resistance

This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This reviewalso summarizes the main resistancemechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases and AmpC β-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump β-lactams out of the bacterial cell.

Wear resistance of TiAlSiN thin coatings

In the last decades TiAlN coatings deposited by PVD techniques have been extensively investigated but, nowadays, their potential development for tribological applications is relatively low. However, new coatings are emerging based on them, trying to improve wear behavior. TiAlSiN thin coatings are now investigated, analyzing if Si introduction increases the wear resistance of PVD films. Attending to the application, several wear test configurations has been recently used by some researchers. In this work, TiAlSiN thin coatings were produced by PVD Unbalanced Magnetron Sputtering technique and they were conveniently characterized using Scanning Electron Microscopy (SEM) provided with Energy Dispersive Spectroscopy (EDS), Atomic Force Microscopy (AFM), Electron Probe Micro-Analyzer (EPMA), Micro Hardness (MH) and Scratch Test Analysis. Properties as morphology, thickness, roughness, chemical composition and structure, hardness and film adhesion to the substrate were investigated. Concerning to wear characterization, two very different ways were chosen: micro-abrasion with ball-on-flat configuration and industrial non-standardized tests based on samples inserted in a feed channel of a selected plastic injection mould working with 30% (wt.) glass fiber reinforced polypropylene. TiAlSiN coatings with a small amount of about 5% (wt.) Si showed a similar wear behavior when compared with TiAlN reported performances, denoting that Si addition does not improve the wear performance of the TiAlN coatings in these wear test conditions.

Resistance of Aedes aegypti to temephos and adaptive disadvantages

OBJECTIVE To evaluate the resistance of Aedes aegypti to temephos Fersol 1G (temephos 1% w/w) associated with the adaptive disadvantage of insect populations in the absence of selection pressure. METHODS A diagnostic dose of 0.28 mg a.i./L and doses between 0.28 mg a.i./L and 1.40 mg a.i./L were used. Vector populations collected between 2007 and 2008 in the city of Campina Grande, state of Paraíba, were evaluated. To evaluate competition in the absence of selection pressure, insect populations with initial frequencies of 20.0%, 40.0%, 60.0%, and 80.0% resistant individuals were produced and subjected to the diagnostic dose for two months. Evaluation of the development of aquatic and adult stages allowed comparison of the life cycles in susceptible and resistant populations and construction of fertility life tables. RESULTS No mortality was observed in Ae. aegypti populations subjected to the diagnostic dose of 0.28 mg a.i./L. The decreased mortality observed in populations containing 20.0%, 40.0%, 60.0%, and 80.0% resistant insects indicates that temephos resistance is unstable in the absence of selection pressure. A comparison of the life cycles indicated differences in the duration and viability of the larval phase, but no differences were observed in embryo development, sex ratio, adult longevity, and number of eggs per female. CONCLUSIONS The fertility life table results indicated that some populations had reproductive disadvantages compared with the susceptible population in the absence of selection pressure, indicating the presence of a fitness cost in populations resistant to temephos.

Increasing the wear resistance of molds for injection of glass fiber reinforced plastics

Abrasion by glass fibers during injection molding of fiber reinforced plastics raises new challenges to the wear performance of the molds. In the last few decades, a large number of PVD and CVD coatings have been developed with the aim of minimizing abrasion problems. In this work, two different coatings were tested in order to increase the wear resistance of the surface of a mold used for glass fiber reinforced plastics: TiAlSiN and CrN/CrCN/DLC. TiAlSiN was deposited as a graded monolayer coating while CrN/CrCN/DLC was a nanostructured coating consisting of three distinct layers. Both coatings were produced by PVD unbalanced magnetron sputtering and were characterized using scanning electron microscopy (SEM) provided with energy dispersive spectroscopy (EDS), atomic force microscopy (AFM), micro hardness (MH) and scratch test analysis. Coating morphology, thickness, roughness, chemical composition and structure, hardness and adhesion to the substrate were investigated. Wear resistance was characterized through industrial tests with coated samples and an uncoated reference sample inserted in a feed channel of a plastic injection mold working with 30 wt.% glass fiber reinforced polypropylene. Results after 45,000 injection cycles indicate that the wear resistance of the mold was increased by a factor of 25 and 58, by the TiAlSiN and CrN/CrCN/DLC coatings, respectively, over the uncoated mold steel.

Resistance of mice immunized with killed culture trypomastigotes against infection by insect-derived trypomastigotes of Trypanosoma cruzi

Mice immunized with heat or merthiolate-killed culture trypomastigotes of the non-virulent G strain were resistant to the challenge by insect-derived trypomastigotes of the CL strain of Trypanosoma cruzi. No parasitemia was detected, by direct microscopic examination of blood samples, in 90% of immunized mice while all control animals developed a high parasitemia. Trypsinization before heat-inactivation, or fixation with paraformaldehyde, apparently reduced the immunogenicity of the G strain trypomastigotes. Mice immunized with trypomastigotes treated by either of these procedures were not protected against infection by virulent T. cruzi. Analysis of the 13I-labeled surface proteins of G strain trypomastigotes inactivated by the various methods suggests that these components are involved in eliciting protective immunity against T. cruzi infection.

Infectivity of amastigotes of Trypanosoma cruzi

The infectivity amastigotes of Trypanosoma cruzi, isolated from the supernatant of the J774G8 macrophage-like cell line infected with trypomastigotes to normal macrophages in vitro was tested. After a period of 1 h of T. cruzi-macrophage interaction about 2% of the mouse peritoneal macrophages had ingested amastigotes. In contrast 12% of the macrophages had ingested epimastigotes. Treatment of the amastigotes with trypsin did not interfere with their ingestion by macrophages. Once inside the macrophages the amastigotes divided and after some days transformed into trypomastigotes. When i.p. inoculated into mice the amastigotes were highly infective, inducing high levels of parasitaemia and tissue parasitism. As previously described for trypomastigotes, amastigotes were not lysed when incubated in the presence of fresh guinea-pig serum. Contrasting with what has been described for trypomastigotes, the resistance of amastigotes to complement-mediated lysis persisted after treatment with trypsin.

Cell mediated immune response in human antirabies revaccination

The occurrence of secondary cell mediated immune response (CMI) in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue) antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

: acquired resistance in mice by implantation of young irradiated worms into the portal system

In two distinct experiments, immature S. mansoni worms (LE strain, Belo Horizonte, Brazil), aged 20 days, obtained from the portal system of white outbred mice, were irradiated with 14 and 4 Krad, respectively. Afterwards, the worms were directly inoculated into the portal vein of normal mice. Inoculation was performed with 20 irradiated worms per animal. Fifty days after inoculation, the mice that received 4 and 14 Krad-irradiated worms and their respective controls were infected with S. mansoni cercariae (LE strain), by transcutaneous route. Twenty days after this challenge infection, the animals were sacrificed and perfused for mature irradiated (90-day-old) and immature (20-day-old) worm counts. Analysis of the results showed that statistically significant protection against cercariae occurred in both groups with irradiated worms.

Probing key DNA contacts in AraR-mediated transcriptional repression of the Bacillus subtilis arabinose regulon.

Nucleic Acid Research (2007) Vol.37 N. 14 4755-4766