Practical consensus recommendaton for adjuvant bone-modifying agents in breast cancer.

Bone-modifying therapy is a primary research interest in breast cancer. Several features contribute to the importance of the bone environment in the management of breast cancer. Firstly, bone metastases represent the most common site of breast cancer metastases and secondly, the emergence of cancer treatment-induced bone loss (CTIBL) among breast cancer survivors and patients is of increasing concern. In the adjuvant setting, bisphosphonates can be given to prevent and treat tumor therapy-induced bone loss in premenopausal and postmenopausal women and, owing to their beneficial effect on bone turnover, have also been evaluated for prevention of bone metastases occurrence. Expert oncologists discusses on the update on the approaches of Bone-modifying Agents and its treatment options. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Acid/base triggered interconversion of µ-η2:η2-peroxido and bis(µ-oxido) dicopper intermediates capped by proton-responsive ligands.

CuII2(µ-η2:η2-peroxido) and CuIII2(µ-oxido)2 cores represent key intermediates in copper/dioxygen chemistry, and they are mechanistically important for biological hydroxylation and oxidation reactions mediated by dinuclear (type III) copper metalloenzymes. While the exact nature of the active species in different enzymes is still under debate, shifting equilibria between Cu x /O2 species is increasingly recognized as a means of switching between distinct reactivity patterns of these intermediates. Herein we report comprehensive spectroscopic, crystallographic and computational analysis of a family of synthetic CuII2(µ-η2:η2-peroxido) and CuIII2(µ-oxido)2 dicopper complexes with a bis(oxazoline) (BOX) capping ligand. In particular, we demonstrate that a reversible peroxido/bis(µ-oxido) interconversion of the [Cu2O2] core can be triggered by peripheral (de)protonation events on the ligand backbone. As the copper ions in the enzymes are typically supported by histidine imidazoles that offer a backside N atom amenable to potential (de)protonation, it is well conceivable that the shifting of equilibria between the [Cu2O2] species in response to changes in local pH is biologically relevant.

Statistical medium optimization and production of a hyperthermostable lipase from Burkholderia cepacia in a bioreactor.

AIM: Statistical medium optimization for maximum production of a hyperthermostable lipase from Burkholderia cepacia and its validation in a bioreactor. METHODS AND RESULTS: Burkholderia cepacia was grown in shake flasks containing 1% glucose, 0.1% KH2PO4, 0.5% NH4Cl, 0.24% (NH4)2HPO4, 0.01% MgSO4.7H2O and 1% emulsified palm oil, at 45 degrees C and pH 7.0, agitated at 250 rev min(-1) with 6-h-old inoculum (2% v/v) for 20 h. A fourfold enhancement in lipase production (50 U ml(-1)) and an approximately three fold increase in specific activity (160 U mg(-1)) by B. cepacia was obtained in a 14 litre bioreactor within 15 h after statistical optimization following shake flask culture. The statistical model was obtained using face centred central composite design (FCCCD) with five variables: glucose, palm oil, incubation time, inoculum density and agitation. The model suggested no interactive effect of the five factors, although incubation period, inoculum and carbon concentration were the important variables. CONCLUSIONS: The maximum lipase production was 50 U ml(-1), with specific activity 160 U mg(-1) protein, in a 14 litre bioreactor after 15 h in a medium obtained after statistical optimization in shake flasks. Further, the model predicted reduction in time for lipase production with reduction in total carbon supply. SIGNIFICANCE AND IMPACT OF THE STUDY: Statistical optimization allows quick optimization of a large number of variables. It also provides a deep insight into the regulatory role of various parameters involved in enzyme production.

Propionic acid production in an in situ cell retention bioreactor.

Continuous fermentations were conducted with in situ cell retention using spin filters (pore size 5 microm and 10 microm) for propionic acid production by Propionibacterium acidipropionici. Continuous fermentation with a 5-microm pore size spin filter resulted in 50% cell retention. Propionic acid productivity was enhanced (0.9 g l(-1) h(-1)) by approximately four-fold compared to conventional batch fermentation (0.25 g l(-1) h(-1)). The in situ cell retention (5-microm pore size spin filter) bioreactor was operated continuously and smoothly for 8 days at a dilution rate of D=0.05 h(-1).

Whiplash injury associated with acute bilateral internal carotid arterial dissection.

Internal carotid arterial occlusion, being a rare occurrence following whiplash injury, is frequently missed. We report an unusual case of a 41-year-old woman driver who was involved in a head-on collision with a truck. On admission she was noted to have sustained closed head and neck trauma with a severe whiplash injury and lower limb paraparesis. Subsequent investigations showed a right parietal lobe infarct and bilateral internal carotid arterial dissection. We conclude that acute whiplash injury can result in bilateral internal carotid arterial dissection and that clinicians treating these patients should be aware of this complication.

A preliminary assessment of possible mutagenicity of betel nut and ingredients of the betel quid when administered alone or in combinations to larvae of Drosophila melanogaster.

The "carcinogenic" betel nut and constituents of betel quid were tested for possible mutagenicity in Drosophila. The test compounds were administered either alone or in combinations by larval feeding. The data on sex-chromosome loss, sex-linked recessive lethals and autosomal translocations suggest lack of mutagenicity.