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BACKGROUND: Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity. METHODS: In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered. RESULTS: Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10–1.71), P = 0.02; PlGF 3.78 (1.30–11.0), P = 0.047; GDF-15 1.71 (1.15–2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions. CONCLUSIONS: Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.

The photosynthetic characteristics of prokaryotic phycoerythrin-rich populations of cyanobacteria Synechococcus spp. and larger eukaryotic algae were compared at a neritic frontal station (Pl), in a warm-core eddy (P2), and at Wilkinson's Basin (P3) during a cruise in the Northwest Atlantic Ocean in the summer of 1984. Synechococcus spp. numerically dominated the 0.6 to 1 μm fraction, and to a lesser extent the 1 to 5 μm size fractions, at most depths at all stations. At P2 and P3, all three size categories of phytoplankton (0.6 to 1 μm, 1 to 5 μm, and >5 μm) exhibited similar depth-dependent chages in both the timing and amplitude of diurnal periodicities of chlorophyllbased and cell-based photosynthetic capacity. Midday maxima in photosynthesis were observed in the upper watercolumn which damped-out in all size fractions sampled just below the thermocline. For all size fractions sampled near the bottom of the euphotic zone, the highest photosynthetic capacity was observed at dawn. At all depths, the Synechococcus spp.-dominated size fractions had lower assimilation rates than larger phytoplankton size fractions. This observation takes exception with the view that there is an inverse size-dependency in algal photosynthesis. Results also indicated that the size-specific contribution to potential primary production in surface waters did not vary appreciably over the day. However, estimates of the percent contribution of Synechococcus spp. to total primary productivity in surface waters at the neritic front were significantly higher when derived from short-term incubator measurements of photosynthetic capacity rather than from dawn-to-dusk in situ measurements of carbon fixation. The discrepancy was not due to photoinhibitory effects on photosynthesis, but appeared to reflect increased selective grazing pressure on Synechococcus spp. in dawn-to-dusk samples. Low-light photoadaptation was evident in analyses of the depth-dependency of P-I parameters (photosynthetic capacity, P; light-limited slope, alpha; P alpha, I; light-intensity beyond which photoinhibition occurs, I) of the > 0.6 μm communities at all three stations and was attributable to stratification of the water column. There was a decrease in assimilation rates and I with depth that was associated with increases in light-limited rates of photosynthesis. No midday photoinhibition of P or I was observed in any surface station. Marked photoinhibition was detected only in the chlorophyll maximum at the neritic front and below the surface mixed-layer at Wilkinson's Basin, where susceptibility to photoinhibition increased with the depth of the collected sample. The 0.6 to 1 μm fraction always had lower light requirements for light-saturated photosynthesis than the > 5 μm size fraction within the same sample. Saturation intensities for the 1 to 5 μm and 0.6 to 1 μm size fractions were more similar when Synechococcus spp. abundances were high in the 1 to 5 μm fraction. The > 5 μm fraction appeared to be the prime contributor to photoinhibitory features displayed in mixed samples (> 0.6 μm) taken from the chlorophyll maxima. In Synechococcus spp.-dominated 0.6 to 1 and 1 to 5 μm size fractions, cellular chlorophyll a content increased 50- to 100-fold with depth and could be related to increases in maximum daytime rates of cellular P at the base of the euphotic zone. Furthermore, the 0.6 to 1 μm and > 5 μm fractions sampled at the chlorophyll maximum in the warm-core eddy had lower light requirements for photosynthesis than comparable surface samples from the same station. Results suggest that photoadaptation in natural populations of Synechococcus spp. is accomplished primarily by changing photosynthetic unit number, occuring in conjuction with other accommodations in the efficiency of photosynthetic light reactions. [ABSTRACT FROM AUTHOR]

Dissolution tests using human enamel were conducted after treatment with aqueous solutions of various aluminum (Al) salts. All Al compounds, except those which formed stable Al-complexes, greatly decreased enamel dissolution in a pH 4 acetate buffer. A comparison with fluoride compounds demonstrated that Al was equivalent to SnF2 and more effective than NaF and Na22PO3F. Furthermore, the reduction in enamel dissolution produced by Al persisted after more than three hr of successive demineralization, which was twice as long as that observed with a pH 4.5 SnF2 solution. [ABSTRACT FROM AUTHOR]