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  • Author: R.W. Davis x
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Abstract

We studied the possibility of an etiological role for endothelin-1 (ET-1) in the development of persistent pulmonary hypertension of the newborn (PPHN). Ten infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) were studied. Pre and post pulmonary blood samples were obtained on commencing ECMO and on recovery. The samples were analyzed by radio-immunoassay. The infants with PPHN requiring ECMO had a significantly higher mean ET-1 concentration (21.1 pmol/l, S. D. 3.59) than a group of healthy controls (16.6 pmol/l, S. D. 4.44); however 8 of our 10 infants had individual ET-1 levels within our reference range for healthy newborns. Pre and post pulmonary ET-1 levels did not differ significantly and there was no evidence of a decline in ET-1 levels with resolution of PPHN. Pulmonary overproduction of ET-1 does not appear to be the cause of PPHN, although the endothelin system may still play a role in the pathophysiology of PPHN, probably mediated through changes in receptor expression.

Abstract

Maximising dairy industry profitability involves maximising product returns for a specific set of costs or minimising costs for a certain level of output. A strategy currently utilised by the New Zealand dairy industry to optimise the value of exports is to incorporate imported lactose along with local milk to maximise the production of whole milk powder (WMP) while complying with the Codex Alimentarius (Codex) standards, in addition to increasing the exported product for every litre of milk. This study investigated the impact of different product portfolio strategies on lactose requirements for the Irish and New Zealand dairy industries for current and predicted 2020 milk output projections. A mass balance processing sector model that accounts for all inputs, outputs and losses involved in dairy processing was used to simulate the processing of milk into WMP, skim milk powder (SMP), cheese, butter and fluid milk of different proportions. All scenarios investigated projected an increase in production and revenue from 2012 to 2020. Higher cheese production reduced industry lactose demand through whey processing, while scenarios reliant on an increase in the proportion of WMP were associated with increased lactose deficits.

Abstract

The bond-valence model has, for several decades, been widely used for creating quantitative structure-activity relationships (QSARs), crystal structure modeling, and verification of proposed structures. Certain limitations of the model, such as the neglect of interactions between cations and between anions, have prevented it from being more broadly applied. In this work, we use cation-cation and anion-anion bonds to augment the existing bonding model in the systems H-Al-Si-O and K-Al-Si- O. The bond valence-length curves for these interactions employ the same mathematical form as ionic bonds, but make only a small contribution to the overall bonding in ionic materials. In the systems examined here, oxygen-oxygen interactions were much more important than those between cations for producing accurate bond-valence sums. Both anion-anion and cation-cation bonding could prove important, however, for our ultimate goal of producing valence-based force fields for use in molecular dynamics simulations. Rolling these interactions into the bond-valence framework would produce behavior similar to hard-sphere repulsive or van der Waals terms, but would more flexibly account for the complete bonding environment. The overall improvement in valence sums was robust, was maintained outside the calibration set, and was invariant to elemental substitution. We conclude that this minor alteration of the bond-valence approach will significantly improve bond-valence models in conjunction with other recent extensions of the approach.

We have demonstrated that the borono-Mannich reaction is a versatile and efficient reaction for the diastereoselective preparation of chiral 1,2-amino alcohols. These Mannich products are valuable starting materials as shown in this report by the synthesis of bioactive polyhydroxylated pyrrolizidine and indolizidine alkaloids. Initial studies, directed at the more complex Stemona alkaloids and using the borono-Mannich reaction on cyclic N-acyliminium ions, are encouraging, as demonstrated by the synthesis of the pyrido[1,2-a]azepine core structure of stemocurtisinol.

Abstract

Photodynamic therapy (PDT) is a treatment modality that uses a specific photosensitizing agent, molecular oxygen, and light of a particular wavelength to kill cells targeted by the therapy. Topically administered aminolevulinic acid (ALA) is widely used to effectively treat cancerous and precancerous skin lesions, resulting in targeted tissue damage and little to no scarring. The targeting aspect of the treatment arises from the fact that ALA is preferentially converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the amount of PpIX in tissues, techniques have been developed to measure PpIX-specific fluorescence, which provides information useful for monitoring the abundance and location of the photosensitizer before and during the illumination phase of PDT. This review summarizes the current state of these fluorescence detection techniques. Non-invasive devices are available for point measurements, or for wide-field optical imaging, to enable monitoring of PpIX in superficial tissues. To gain access to information at greater tissue depths, multi-modal techniques are being developed which combine fluorescent measurements with ultrasound or optical coherence tomography, or with microscopic techniques such as confocal or multiphoton approaches. The tools available at present, and newer devices under development, offer the promise of better enabling clinicians to inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes for patients.