The combination of trimethoprim and sulfamethoxazole in the treatment of urinary tract infection

In a series of 52 patients the combination of trimethoprim and sulfamethoxazole was used for the treatment of urinary tract infection and the results are analyzed with respect to the clinical diagnosis and bacterial etiology. There was complete agreement between in vitro sensitivity and clinical response except in the case of one strain of Streptococcus fecalis. The combination of drugs was effective against some bacterial strains which were resistant to the commonly used antimicrobial agents.     

Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H₂O₂) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H₂O₂ against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H₂O₂ to PAA formation. This study confirmed the synergistic activity of the combination of H₂O₂ and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H₂O₂. Furthermore, we observed that the synergistic combination was based on H₂O₂ compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity.     

LPS-induced biomarkers in mice: a potential model for identifying insulin sensitizers

The contribution of nutrient overload and associated inflammation to insulin resistance has highlighted several therapeutic targets including c-Jun N-terminal kinase (JNK) and S6 kinase (S6K). To investigate how a lipopolysaccharide (LPS)-mediated inflammatory response may modulate pathways implicated in insulin resistance, we characterized the LPS-induced changes in key biomarkers. Administration of 0.06-4 mg/kg LPS to C57BL/6 mice stimulated increases in plasma levels of TNFalpha, IL-12p40, IL-6 and MCP-1 and in JNK activity as measured by phosphorylated c-Jun in fat. For the first time, we show that LPS induces S6K activity by up to 6.1-fold, as measured by the phosphorylation of S6 ribosomal protein in liver, and increases by up to 1.8-fold, plasma levels of the novel pro-inflammatory cytokine osteopontin which is implicated in the pathogenesis of insulin resistance. These novel findings suggest that LPS administration may form the basis of an acute in vivo pharmacodynamic model for therapies targeting multiple pathways implicated in insulin resistance.     

A Cascading Auction Protocol as a Framework for Integrating Process Planning and Heterarchical Shop Floor Control

A new contract net-style auction protocol is proposed as a framework for integrating process planning and shop floor control in heterarchical manufacturing systems. Process planning is partitioned into on-line and off-line activities; off-line process planning decisions are represented in a graph format and used as input for on-line process planning activities performed by machine controllers. Triggered by the opening round of an auction, the final on-line stages of process planning are dovetailed with the resource allocation process in the shop floor control system. The auction process allows final process planning decisions to be based on timely information, relying on the distribution of static process planning information rather than the distribution of a model of dynamic shop floor status and allowing a controller to identify all the primary and secondary resources and operations that must be provided for the incremental processing of a part.     

Evidence for autosomal dominant inheritance of prostate cancer.

A family-history cancer survey was conducted on 5,486 men who underwent a radical prostatectomy, for clinically localized prostate cancer, in the Department of Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey. Complex segregation analysis was performed to assess the genetic basis of age at diagnosis and the familial clustering of prostate cancer. For the total group, no single-gene model of inheritance clearly explained familial clustering of disease, which could be partly explained by lack of Hardy-Weinberg equilibrium, with an excess of homozygotes. After accounting for deviations from Hardy-Weinberg equilibrium, the best-fitting model that explained the familial aggregation and age at diagnosis was a rare autosomal dominant susceptibility gene, and this model fitted best when probands were diagnosed at <60 years of age. The model predicts that the frequency of the susceptibility gene in the population is .006 and that the risk of prostate cancer by age 85 years is 89% among carriers of the gene and 3% among noncarriers. A strength of our study is its large size, such that genetic models could be fitted within strata defined by the age of the proband. Although the autosomal dominant model was consistently the best model, the parameter estimates differed somewhat (P=.03) across the different age groups, suggesting genetic heterogeneity. Additional evidence that the hereditary basis of prostate cancer is likely to be genetically complex was provided by the following: (1) there was a significantly elevated age-adjusted risk of prostate cancer among brothers of probands, compared with their fathers (relative risk 1.5 [95% confidence interval 1.4-1.7]); (2) the autosomal dominant model predicted an excess of homozygotes, over that predicted by Hardy-Weinberg equilibrium; and (3) the model-predicted risk of prostate cancer among relatives was inadequate when probands were diagnosed at age >=70 years.     

Functional trait changes in the floras of 11 cities across the globe in response to urbanization

Urbanization causes major environmental changes globally, which can potentially homogenize biota across cities through the loss and gain of particular types of species. We examine whether urban environments consistently select for plants with particular traits and the implications of such changes on the functional composition of urban floras. We classified plant recorded in 11 cities around the globe as species that have either colonized (arrived and naturalized), persisted or been lost (local extirpation) following urbanization. We analyzed how 10 traits previously linked with plant responses to environmental conditions explained membership of these three groups, by comparing colonisers with persistent and extirpated plants through individual city‐level Bayesian models. Then, we used meta‐analysis to assess consistency of traits across urban areas. Finally, we explored several possible scenarios of functional change using these results. On average, urban colonizers had heavier seeds, unspecialised nutrient requirements, were taller and were annual species more often, especially when compared to locally extirpated plants. Common trends of functional change in urban plant communities include shifts towards taller and heavier‐seeded plants, and an increased prevalence of the short‐lived species, and plants without mutualistic nutritional strategies. Our results suggest that plant traits influence the species that succeed in urban environments worldwide. Different species use different ecological strategies to live in urban environments, as suggested by the importance of several traits that may appear as trait constellations. Plant height and seed mass were the only traits associated with both colonizer and extirpated plant status in urban environments. Based on our data, predicting colonization in urban environments may be easier than identifying extirpation‐prone plants; albeit some regional variation, colonization seems strongly driven by environmental conditions common to most cities (e.g. altered disturbance regimes), whereas extirpation may depend more on processes that vary across cities.     

Bone marrow-derived endothelial progenitor cells contribute to the angiogenic switch in tumor growth and metastatic progression

Emerging evidence indicates that bone marrow (BM)-derived endothelial progenitor cells (EPCs) contribute to angiogenesis-mediated growth of certain tumors in mice and human. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. While the contributions of EPCs to neovessel formation in spontaneous and transplanted tumors and to the metastatic transition have been reported to be relatively low, remarkably, specific EPC ablation in vivo has resulted in severe angiogenesis inhibition and impaired primary and metastatic tumor growth. The existence of a BM reservoir of EPCs, and the selective involvement of EPCs in neovascularization, have attracted considerable interest because these cells represent novel target for therapeutic intervention. In addition, EPCs are also being used as pharmacodynamic surrogate markers for monitoring cancer progression, as well as for optimizing efficacy of anti-angiogenic therapies in the clinic. This review will focus primarily on recent advances and emerging concepts in the field of EPC biology and discuss ongoing debates involving the role of EPCs in tumor neovascularization. For detailed information on the in vitro characterization of EPCs contribution to non-tumor pathologies, the reader is directed towards several excellent reviews and publications [F. Bertolini, Y. Shaked, P. Mancuso and R.S. Kerbel, Nat. Rev., Cancer 6 (2006) 835–845. [1]] [J.M. Hill, T. Finkel and A.A. Quyyumi, Vox Sang. 87 Suppl 2 (2004) 31–37. [2]] [A.Y. Khakoo and T. Finkel, Annu. Rev. Med. 56 (2005) 79–101. [3]] [H.G. Kopp, C.A. Ramos and S. Rafii, Curr. Opin. Hematol. 13 (2006) 175–181. [4]; K.K. Hirschi, D.A. Ingram and M.C. Yoder, Arterioscler. Thromb. Vasc. Biol. 28 (2008) 1584–1595. [5]; F. Timmermans, J. Plum, M.C. Yoder, D.A. Ingram, B. Vandekerckhove and J. Case, J. Cell. Mol. Med. 13 (2009) 87–102. [6]] and reviews by Bertolini, Voest and Yoder in this issue.