New Metabolites of Streptomyces alboniger

A mutant unable to grow under acidic conditions was isolated from the acidophilic heterotrophic bacterium Acidiphilium facilis 24R. The growth of the mutant could be fully restored by the addition of spermidine or lysine at the concentration of 100 μm. The HPLC analysis of polyamine composition showed that spermidine and putrescine were major polyamine components in the parental strain. In the mutant strain, putrescine was replaced by cadaverine. It was found that some polyamines in the cells were conjugated with the other cell components. The growth of the bacterium in the medium below pH 4.5 was inhibited in the presence of α-methylornithine or methylglyoxal-bis(guanylhydrazone), which are inhibitors of rate-limiting enzymes involved in the biosynthesis of polyamines. The growth of the bacterium that had been inhibited in the presence of inhibitors could be fully restored by the addition of putrescine or spermidine. On the basis of these results, it was concluded that polyamines have a significant role in the growth of Acidiphilium facilis 24R under acidic conditions.     

Phase II Study of Concurrent Capecitabine and External Beam Radiotherapy for Pain Control of Bone Metastases of Breast Cancer Origin

Background

Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer.

Methodology/Principal Findings

Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m² twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial) at 12 weeks was 86%. Side effects were of mild intensity (grade I or II) and included nausea (38% of patients), weakness (24%), diarrhea (24%), mucositis (10%), and hand and foot syndrome (7%).

Conclusions/Significance

External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01784393","term_id":"NCT01784393"}}NCT01784393{"type":"clinical-trial","attrs":{"text":"NCT01784393","term_id":"NCT01784393"}}NCT01784393     

The DNA damage response mediator MDC1 directly interacts with the anaphase-promoting complex/cyclosome

MDC1 (NFBD1), a mediator of the cellular response to DNA damage, plays an important role in checkpoint activation and DNA repair. Here we identified a cross-talk between the DNA damage response and cell cycle regulation. We discovered that MDC1 binds the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that controls the cell cycle. The interaction is direct and is mediated by the tandem BRCA1 C-terminal domains of MDC1 and the C terminus of the Cdc27 (APC3) subunit of the APC/C. It requires the phosphorylation of Cdc27 and is enhanced after induction of DNA damage. We show that the tandem BRCA1 C-terminal domains of MDC1, known to directly bind the phosphorylated form of histone H2AX (gamma-H2AX), also bind the APC/C by the same mechanism, as phosphopeptides that correspond to the C termini of gamma-H2AX and Cdc27 competed with each other for the binding to MDC1. Our results reveal a link between the cellular response to DNA damage and cell cycle regulation, suggesting that MDC1, known to have a role in checkpoint regulation, executes part of this role by binding the APC/C.     

Terrorism, trauma, and mass casualty triage: how might we solve the latest mind-body problem?

The global war on terrorism has led to increased concern about the ability of the U.S. healthcare system to respond to casualties from a chemical, biological, or radiological agent attack. Relatively little attention, however, has focused on the potential, in the immediate aftermath of such an attack, for large numbers of casualties presenting to triage points with acute health anxiety and idiopathic physical symptoms. This sort of "mass idiopathic illness" is not a certain outcome of chemical, biological, or radiological attack. However, in the event that this phenomenon occurs, it could result in surges in demand for medical evaluations that may disrupt triage systems and endanger lives. Conversely, if continuous primary care is not available for such patients after initial triage, many may suffer with unrecognized physical and emotional injuries and illness. This report is the result of an expert planning initiative seeking to facilitate triage protocols that will address the possibility of mass idiopathic illness and bolster healthcare system surge capacity. The report reviews key triage assumptions and gaps in knowledge and offers a four-stage triage model for further discussion and research. Optimal triage approaches offer flexibility and should be based on empirical studies, critical incident modeling, lessons from simulation exercises, and case studies. In addition to staging, the proposed triage and longitudinal care model relies on early recognition of symptoms, development of a registry, and use of non-physician care management to facilitate later longitudinal followup and collaboration between primary care and psychiatry for the significant minority of patients who develop persistent idiopathic symptoms associated with reduced functional status.     

Biology of Bactrocera carambolae (Diptera: Tephritidae) on four hosts

Bactrocera carambolae is a quarantine pest found in Brazil, restricted to the states of Amapá, Pará and Roraima. This fruit fly can potentially cause extensive socioeconomic and environmental damage in the country, if it disperse into areas where fruit is grown for exporting. The objective of this work was to study the biology of B. carambolae on fruits of Averrhoa carambola L. (Oxalidaceae), Psidium guajava L. (Myrtaceae), Spondias mombin L. (Anacardiaceae) and Eugenia stipitata McVaugh (Myrtaceae). The following parameters were investigated: duration of egg-larva, pupal, egg-adult, pre-oviposition, oviposition and post-oviposition periods, pupal weight and viability, sex ratio, fecundity, fertility and longevity. All parameters except pupal weight, oviposition and post-oviposition period, egg fertility and sex ratio were influenced by the host plant on which the larvae were reared. The carambola fruit fly completes its development on all those hosts studied here, with the highest fecundities on A. carambola and P. guajava.