BackgroundMultidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence...Full Text Available
BackgroundAurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently...Full Text Available
Purpose of reviewPhysicians, researchers and policy makers must understand the myriad consequences of multidrug and extensively drug-resistant tuberculosis (TB) within...Full Text Available
The emergence of Escherichia coli that produce extended spectrum β-lactamases (ESBLs) and are multidrug resistant (MDR) poses antibiotic management problems....Full Text Available
Eribulin is a new anticancer agent currently in Phase III clinical trials for the treatment of metastatic breast cancer. In the current studies, we have investigated the effects of P-glycoprotein (P-gp) on the in vivo disposition of eribulin using CF-1 abcb1a-deficient mice, and the influence of eribulin on P-gp-mediated efflux of digoxin in Caco-2 cells. Eribulin was administered intravenously and orally in both CF-1 wild-type and CF-1 abcb1a-deficient mice. P-gp-mediated efflux of digoxin in Caco-2 cell monolayers was measured in the presence of eribulin. The plasma exposure to eribulin was higher in CF-1 abcb1a-deficient mice than that in CF-1 wild-type mice after intravenous (IV) and oral (PO) administrations. The oral bioavailability of eribulin was 62.3% in CF-1 abcb1a-deficient mice...
BACKGROUNDNew diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid,...Full Text Available
Contact precautions are implemented to reduce transmission of multidrug-resistant organisms but may also increase hospital costs and patient complications. The goal of this study was to determine...Full Text Available
For rapid and low-cost detection of multidrug-resistant (MDR) Mycobacterium tuberculosis, we applied the nitrate reductase assay (NRA) using a liquid medium directly to sputum samples....Full Text Available
The multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including β-lactams. However, the kinetic constants of the efflux process, needed for the quantitative...Full Text Available
ColV plasmids of extraintestinal pathogenic Escherichia coli (ExPEC) encode a variety of fitness and virulence factors and have long been associated with septicemia and avian colibacillosis....Full Text Available
Over the past 10 years, the Peruvian National Tuberculosis (TB) Program, the National Reference Laboratory (NRL), Socios en Salud, and US partners have worked to strengthen the national TB laboratory...Full Text Available
Multidrug-resistant tuberculosis is an increasing public health concern in many parts of the world, especially in low-income countries, where most cases occur. Traditional drug susceptibility testing...Full Text Available
IntroductionKluyvera ascorbata has become increasingly significant due to its potential to cause a wide range of infections, as well as its ability to transfer gene...Full Text Available
Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella...Full Text Available
Infection due to multidrug resistance pathogens is difficult to manage due to bacterial virulence factors and because of a relatively limited choice of antimicrobial agents. Thus, it is imperative to...Full Text Available
Background The scale-up of treatment for HIV and multidrug-resistant tuberculosis (MDR-TB) in developing countries requires a long-term relationship with the...Full Text Available
Current methods for drug susceptibility testing of Mycobacterium tuberculosis are either costly or slow. As the prevalence of multidrug-resistant strains increases, the need for fast,...Full Text Available
The Gram-negative bacterium Francisella tularensis is the causative agent of tularemia. Interest in this zoonotic pathogen has increased due to its classification as a category A agent...Full Text Available
BackgroundThe emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to...Full Text Available
The expression of tripartite multidrug efflux pumps such as MexA-MexB-OprM in Pseudomonas aeruginosa contributes to intrinsic resistance to a wide variety of antimicrobials, including...Full Text Available
PurposeCoexistence of different classes of β-lactamases in a single bacterial isolate may pose diagnostic and therapeutic challenges. We investigated a spread of Klebsiella...Full Text Available
SummaryA laboratory-based surveillance study was conducted from January 2007 to May 2010 in San Martino Tertiary Referral Hospital in Genoa, Italy in which the molecular epidemiology of multidrug-resistant Acinetobacter baumannii was investigated in the five intensive care units (ICUs). A total of 53 A. baumannii strains were isolated from patients admitted to ICUs (69.8%) and to other epidemiologically linked hospital wards (30.2%) and were genotyped by repetitive extragenic palindromic polymerase chain reaction (REP-PCR), multilocus sequence typing (MLST) and adeB sequence typing. REP-PCR fingerprinting analysis, MLST and adeB typing results were well correlated and allowed us to classify strains causing epidemic events into three major epidemic clones: A (REP-I/ST4, adeB-STII genotype) ...
Summary.? It is widely believed that hepatocellular cancer (HCC), especially HBV associated HCC, is highly resistant to chemotherapy. To investigate the molecular influence of HBx protein on multidrug resistance (MDR) in HCC and the potential role of the NF-?B pathway in this process. We established HBx-expressing cells by liposome-mediated transfection of the HBx into the HepG2 cell line. We found that HBx expression in HCC cells induces drug resistance against multiple drugs, a significantly lower apoptosis ratio in HepG2-HBx and HepG2.2.15 cells, compared with HepG2 and HepG2-3.1 cells (P?HCC cells were downregulated by IMD-0354 treatment, which is the NF-?B pathway inhibitor. Taken together, these results suggest that HBx protein might be one of the causes for the occurrence of MDR in HCC, and the NF-?B pathway might be involved in this change. PMID:21914061
The existence of a narrow peak in the electronic density of states in A-15 compounds is explained by a strong electron--phonon interaction that leads to the polaron narrowing of the band. An analytic expressionrelating the transition temperature T/sub c/ to the phonon spectrum is derived under the assumption of a weak and an intermediate-strength coupling. The model allows the explanation of the correlation of T/sub c/ with the number of electrons per atom, the temperature dependence of the resistance, the magnitude and temperature dependence of the magnetic susceptibility, and the electronic specific heat.
The world of antibiotic drug discovery and development is driven by the necessity to overcome antibiotic resistance in common Gram-positive and Gram-negative pathogens. However, the lack of Gram-negative activity among both recently approved antibiotics and compounds in the developmental pipeline is a general trend despite the fact that the plethora of covered drug targets are well-conserved across the bacterial kingdom. Such intrinsic resistance in Gram-negative bacteria is largely attributed to the activity of multidrug resistance (MDR) efflux pumps. Moreover, these pumps also play a significant role in acquired clinical resistance. Together, these considerations make efflux pumps attractive targets for inhibition in that the resultant efflux pump inhibitor (EPI)/antibiotic combination d...
Summary This third paper, in a three-part CE series on the preventions of infection in patients with chronic kidney disease, focuses on surveillance and auditing of healthcare-associated infections within the renal care environment. The last decade has seen an increased awareness of the threat to patient safety from healthcare-associated infection (HCAI) and the emergence of multi-drug resistance organisms. Effective HCAI prevention strategies include adequate governance structures, access to expert advice, adherence to standard and transmission-based precautions, minimising the use of invasive medical devices, and surveillance. Surveillance data can be collected using outcome (e.g. infection) and/or process (e.g. hand hygiene compliance audit) measures. Establishing a surveillance program...
Abstract NorUDCA (24 norursodeoxycholic acid), the C23 homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine conjugated UDCA (C24) and norUDCA (C23) in isolated perfused rat liver (IPRL) and in natrium/taurocholate cotransporting polypeptide (Ntcp) transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predomi...
Abstract:- Campylobacter jejuni-is the leading cause of bacterial diarrheal illness worldwide. Many strains are now becoming multidrug resistant. Apple-based edible films containing carvacrol and cinnamaldehyde were evaluated for bactericidal activity against antibiotic resistant and susceptible-C. jejuni-strains on chicken. Retail chicken breast samples inoculated with D28a and H2a (resistant strains) and A24a (a sensitive strain) were wrapped in apple films containing cinnamaldehyde or carvacrol at 0.5%, 1.5%, and 3% concentrations, and then incubated at 4 or 23 C for 72 h. Immediately after wrapping and at 72 h, samples were plated for enumeration of viable-C. jejuni. The antimicrobial films exhibited dose- and temperature-dependent bactericidal activity against all strains. Films with ...
Tripartite efflux systems are responsible for the export of toxins across both the inner and outer membranes of Gram negative bacteria. Previous work has indicated that EmrAB-TolC from Escherichia coli is such a tripartite system, comprised of EmrB an MFS transporter, EmrA, a membrane fusion protein and TolC, an outer membrane channel. The whole complex is predicted to form a continuous channel allowing direct export from the cytoplasm to the exterior of the cell. Little is known, however, about the interactions between the individual components of this system. Reconstitution of EmrA + EmrB resulted in co-elution of the two proteins from a gel filtration column indicating formation of the EmrAB complex. Electron microscopic single particle analysis of the reconstituted EmrAB complex revealed the presence of particles approximately 240 x 140 A, likely to correspond to two EmrAB dimers in a back-to-back arrangement, suggesting the dimeric EmrAB form is the physiological state contrasting ...
BACKGROUND: Although definitions vary, infected nonunion has been defined as a state of failure of union and persistence of infection at the fracture site for 6 to 8 months.>). Infected nonunions of the supracondylar region of the femur are uncommon and are mostly due to a severe open fracture with extensive comminution and segmental bone loss or after internal fixation of a comminuted closed fracture. Associated factors include exposed bone devoid of vascularized periosteal coverage for more than 6 weeks, purulent discharge, a positive bacteriological culture from the depth of the wound, and histologic evidence of necrotic bone containing empty lacunae. Soft-tissue loss with multiple sinuses, osteomyelitis, osteopenia, complex deformities with limb-length inequality, stiffness of the adjacent joint, polybacterial multidrug-resistant infection, and smoking all complicate treatment and recovery. Although uncommon in incidence, infected nonunions of the long bones ...
From 1981 up to February 1985, a total of 93 protocol patients entered the study CESS 81. The protocol recommended an initial 18-week period of polychemotherapy (VACA) followed by local therapy and two additional cycles of chemotherapy. Local therapy consisted either of radical surgery or of incomplete resection plus postoperative irradiation with 36 Gy or of radiotherapy alone (46 and 60 Gy). Centrally located lesions were always irradiated with 60 Gy. This article summarizes the data after 5 years. Data of 93 patients were analysed in October 1986 after a median follow-up of 37 months. The projected 5-year survival is 50%. The relapse rate was 42%, distant relapses occurred in 19%, local (plus distant) relapses in 23%. Most of the relapses occurred during the first 3 years of observation. Failure rate was high in patients undergoing irradiation alone (44%). Initial tumour mass (> 100 ml) and histopathologic response to initial chemotherapy were identified as major prognostic ...
We present the draft genome sequence and its analysis for Fusobacterium nucleatum sub spp. vincentii (FNV), and compare that genome with F. nucleatum ATCC 25586 (FN). A total of 441 FNV open reading frames (ORFs) with no orthologs in FN have been identified. Of these, 118 ORFs have no known function and are unique to FNV, whereas 323 ORFs have functional orthologs in other organisms. In addition to the excretion of butyrate, H2S and ammonia-like FN, FNV has the additional capability to excrete lactate and aminobutyrate. Unlike FN, FNV is likely to incorporate galactopyranose, galacturonate, and sialic acid into its O-antigen. It appears to transport ferrous iron by an anaerobic ferrous transporter. Genes for eukaryotic type serine/threonine kinase and phosphatase, transpeptidase E-transglycosylase Pbp1A are found in FNV but not in FN. Unique ABC transporters, cryptic phages, and three types of restriction-modification systems have been identified in FNV. ORFs for ethanolamine ...
Abstract in english Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide (more) , can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific ...
Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, ...
An overview of the understanding of correlation between valence electron and the optical properties of binary (A{sup N}B{sup 8-N}) and ternary (A{sup N}B{sup 2+N}C{sub 2}{sup 7-N}) tetrahedral semiconductors is presented here. We have presented two expressionsrelating the dielectric constant and electronic polarizability for the transition metal chalcogenides and pnictides (A{sup II}B{sup VI} and A{sup III}B{sup V}) and chalcopyrites (A{sup I}B{sup III}C{sub 2}{sup VI} and A{sup II}B{sup IV}C{sub 2}{sup V}) with the product of valence electrons and nearest neighbour distance d (A). The dielectric constant and electronic polarizability of these solids exhibit a linear relationship when plotted on a log-log scale against the nearest neighbour distance d (A), but fall on different straight lines according to the valence electron product of the compounds. We have applied the proposed relation on these solids and found a better agreement with the ...
Purpose: We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. Methods and Materials: From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk tumors (extremity tumors =# 100 cm"3). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for ...