Effects of the combination of camptothecin and doxorubicin or etoposide on rat glioma cells and camptothecin-resistant variants

From the rat C6 glioma cell line in culture, we selected camptothecin-resistant variants by growth in the presence of increasing amounts of this drug (C6CPT10, C6CPT50 and C6CPT100, growing respectively with 10, 50 and 100 ng ml–1camptothecin). The degree of resistance to camptothecin ranged between 15-fold (C6CPT10) and 30-fold (C6CPT50and C6CPT100). The C6CPT10cell line presented a collateral sensitivity to etoposide (3.6-fold), while the C6CPT50 and C6CPT100 cell lines were cross-resistant to etoposide (1.8-fold) The resistant lines were characterised by a two-fold reduced content and catalytic activity of topoisomerase I, and C6CPT50 and C6CPT100 presented a significant increase in topoisomerase IIα content and catalytic activity and a marked overexpression of P-glycoprotein. We explored the cytotoxicity of combinations of a topoisomerase I inhibitor (camptothecin) and a topoisomerase II inhibitor (doxorubicin or etoposide) at several molar ratios, allowing the evaluation of their synergistic or antagonistic effects on cell survival using the median effect principle. The simultaneous combination of camptothecin and doxorubicin or etoposide was additive or antagonistic in C6 cells, slightly synergistic in the C6CPT10 line and never more than additive in the C6CPT50 and C6CPT100 cell lines. The sequential combination of doxorubicin and camptothecin gave additivity in the order camptothecin → doxorubicin and antagonism in the order doxorubicin → camptothecin. Clinical protocols combining a topoisomerase I and a topoisomerase II inhibitor should be considered with caution because antagonistic effects have been observed with combinations of camptothecin and doxorubicin.© 2001 Cancer Research Campaign http://www.bjcancer.co

As, Pb, Sb, and Zn transfer from soil to root of wild rosemary: do native symbionts matter?

International audienceThis is an in natura study aimed to determine the potential of Rosmarinus officinalis for phytostabilization of trace metal and metalloid (TMM)-contaminated soils in the Calanques National Park (Marseille, southeast of France). The link between rosemary tolerance/accumulation of As, Pb, Sb, and Zn and root symbioses with arbuscular mycorrhizal (AM) fungi and/or dark septate endophytes (DSE) was examined. Eight sites along a gradient of contamination were selected for soil and root collections. TMM concentrations were analyzed in all the samples and root symbioses were observed. Moreover, in the roots of various diameters collected in the most contaminated site, X-ray microfluorescence methods were used to determine TMM localization in tissues. Rosemary accumulated, in its roots, the most labile TMM fraction in the soil. The positive linear correlation between TMM concentrations in soil and endophyte root colonization rates suggests the involvement of AM fungi and DSE in rosemary tolerance to TMM. Moreover, a typical TMM localization in root peripheral tissues of thin roots containing endophytes forming AM and DSE development was observed using X-ray microfluorescence. Rosemary and its root symbioses appeared as a potential candidate for a phytostabilization process of metal-contaminated soils in Mediterranean area

Recurrent outbreaks of Serratia marcescens among neonates and infants at a pediatric department: an outbreak analysis.

PURPOSE: Serratia marcescens is a known cause of bloodstream infections (BSIs) and outbreaks in neonates receiving intensive care. Our aim was to analyze clinical and epidemiological characteristics of two outbreaks detected in our unit to prevent and control further epidemic infections. METHODS: Two episodes of BSI outbreaks in neonates have been investigated in a 20-month period at a pediatric department of a medical university in Hungary. We collected all S. marcescens strains that were isolated in the study period, and two strains that were isolated before the outbreaks. Strains were analyzed by pulsed-field gel electrophoresis (PFGE). Clinical data were collected for the BSIs during and between the outbreaks (n = 14). RESULTS: Out of the 28 S. marcescens isolates investigated by PFGE, 16 were blood isolates. All isolates represented four PFGE types. Pathogenic strains that caused epidemic BSIs were related to a single PFGE type (SM009). Strains with the same pulsotype could be detected before, between, and after the outbreak periods from surveillance cultures of neonates, and a water tap in the infant care unit despite intensive infection control measures. Case fatality rate of BSIs was 29 %. Rate of complications in central nervous system was high: 3/14 neonates developed meningitis. CONCLUSIONS: Rapid spread and high mortality rate of S. marcescens infections necessitate a high suspicion when isolating this species in neonatal intensive care. Early identification of outbreaks is essential, that can be facilitated by determination of clonal relatedness using molecular methods, and with regular surveillance cultures of patients and environment

Diagnosing small bowel malabsorption: a review

Malabsorption encompasses dysfunctions occurring during the digestion and absorption of nutrients. A small proportion of patients presents with chronic diarrhoea. A clinical history supportive of malabsorption may guide investigations toward either the small bowel or pancreas. Serological testing for coeliac disease will determine most cases without invasive investigations. In the clinical context of persisting weight loss and malnutrition, small bowel enteropathy may be investigated with small intestinal biopsies. Small bowel absorptive capacity and permeability might be measured by oral sugar-mix ingestion. Further, approaches to the investigation of malabsorption might also involve the detection in faeces of a substance that has not been absorbed. A variation of the latter is the use of breath testing which relies on the breakdown of the malabsorbed test substance by colonic flora. Measurement of protein absorption is difficult and unreliable; it is, therefore, rarely advocated in clinical settings. No single biological marker confirming a diagnosis of small bowel malabsorption or small bowel integrity is presently available in clinical practice. Plasma citrulline concentration, an amino acid not incorporated into endogenous or exogenous proteins, has been extensively used in research studies and supportive results are establishing its concentration as a reliable quantitative biomarker of enterocyte absorptive capacity