Targeting antibiotic resistance

Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human-pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even lastresort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens

Antibiotikaresistenzen gezielt überwinden

Neue Strategien zur Bekämpfung von Antibiotikaresistenzen zu finden, ist eine der grössten globalen Herausforderungen für die Gesundheitssysteme. In den letzten Jahrzehnten gab es eine drastische Zunahme an humanpathogenen Bakterien, die resistent gegen Antibiotika sind. Immer mehr Infektionen, die durch resistente Mikroorganismen verursacht werden, lassen sich nicht mehr mit konventionellen Behandlungen kurieren, und selbst Reserveantibiotika verlieren ihre Wirkung. Zusätzlich sind die Entwicklungsströme an neuen Antibiotika aus der pharmazeutischen Industrie in den letzten Jahrzehnten versiegt. Die Weltgesundheitsorganisation hat mit ihrem Aufruf „Combat drug resistance: no action today means no cure tomorrow“ eine Zunahme der Forschungsaktivitäten auf diesem Gebiet stimuliert, und mehrere neue,vielversprechende Strategien zur Wiederherstellung antibiotischer Behandlungsoptionen konnten seitdem entwickelt werden

Association of single nucleotide polymorphisms with renal cell carcinoma in Algerian population

Background: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. The etiology of RCC is a complex interaction between environmental and multigenetic factors. Genome-wide association studies have iden? tifed new susceptibility risk loci for RCC. We examined associations of genetic variants of genes that are involved in metabolism, DNA repair and oncogenes with renal cancer risk. A total of 14 single nucleotide polymorphisms (SNPs) in 11 genes (VEGF, VHL, ATM, FAF1, LRRIQ4, RHOBTB2, OBFC1, DPF3, ALDH9A1 and EPAS1) were examined. Methods: The current case?control study included 87 RCC patients and 114 controls matched for age, gender and ethnic origin. The 14 tag-SNPs were genotyped by Sequenom MassARRAY? iPLEX using blood genomic DNA. Results: Genotype CG and allele G of ATM rs1800057 were signifcantly associated with RCC susceptibility (p=0.043; OR=8.47; CI=1.00?71.76). Meanwhile, we found that genotype AA of rs67311347 polymorphism could increase the risk of RCC (p=0.03; OR=2.95; IC=1.10?7.89). While, genotype TT and T allele of ALDH9A1 rs3845536 were observed to approach signifcance for a protective role against RCC (p=0.007; OR=0.26; CI=0.09?0.70). Conclusion: Our results indicate that ATM rs1800057 may have an efect on the risk of RCC, and suggest that ALDH9A1 was a protective factor against RCC in Algerian populatio

Development of osteoblast colonies on new bioactive coatings

The aging baby boomer population coupled with an increase in life expectancy is leading to a rising number of active elderly persons in occidental countries. As a result, the orthopedic implant industry is facing numerous challenges such as the need to extend implant life, reduce the incidence of revision surgery, and improve implant performance. This paper reports results of an investigation on the bioperformance of newly developed coating-substrate systems. Hydroxyapatite (HA) and nano-titania (nano-TiO\u2082) coatings were produced on Ti-6Al-4V and fiber reinforced polymer composite substrates. In vitro studies were conducted to determine the capacity of bioactive coatings developed to sustain osteoblast cells (fetal rat calvaria) adherence, growth, and differentiation. As revealed by scanning electron microscopy (SEM) observations and alkaline phosphatase activity, cell adhesion and proliferation demonstrated that HA coatings over a polymer composite are at least as good as HAcoatings made over Ti-6Al-4V substrate in terms of osteoblast cell activity. Nano-TiO\u2082 coatings produced by high-velocity oxyfuel (HVOF) spraying led to different results. For short-term cell culture (4.5 and 24 h), the osteoblasts appeared more flattened when grown on nano-TiO\u2082 than on HA. The surface cell coverage after seven days of incubation was also more complete on nano-TiO\u2082 than HA. Preliminary results indicate that osteoblast activity after 15 days of incubation on nano-TiO\u2082 is equivalent to or greater than that observed on HA.Peer reviewed: YesNRC publication: Ye

Phosphatidylserine Targets Single-Walled Carbon Nanotubes to Professional Phagocytes In Vitro and In Vivo

Broad applications of single-walled carbon nanotubes (SWCNT) dictate the necessity to better understand their health effects. Poor recognition of non-functionalized SWCNT by phagocytes is prohibitive towards controlling their biological action. We report that SWCNT coating with a phospholipid “eat-me” signal, phosphatidylserine (PS), makes them recognizable in vitro by different phagocytic cells - murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c) allowed for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PS-coating can be utilized for targeted delivery of SWCNT with specified cargoes into professional phagocytes, hence for therapeutic regulation of specific populations of immune-competent cells

Pseudouridimycin : das erste Nukleosid-Analogon, das bakterielle RNA-Polymerase selektiv inhibiert

Gesucht und gefunden: Nach Jahren der Fokussierung auf synthetische Antibiotika konnte jetzt ein neuartiger antibiotischer Wirkstoff durch konventionelles Screening in mikrobiellen Naturstoffextrakten entdeckt werden: Pseudouridimycin (PUM). Der selektive Nukleosid-Analogon-basierte Inhibitor der bakteriellen RNA-Polymerase zeigt ein breites Wirkspektrum und eine geringe Resistenzrate