Cardiac chymase: pathophysiological role and therapeutic potential of chymase inhibitors

On release from cardiac mast cells, alpha-chymase converts angiotensin I (Ang I) to Ang II. In addition to Ang II formation, alpha-chymase is capable of activating TGF-beta 1 and IL-1 beta, forming endothelins consisting of 31 amino acids, degrading endothelin-1, altering lipid metabolism, and degrading the extracellular matrix. Under physiological conditions the role of chymase in the mast cells of the heart is uncertain. In pathological situations, chymase may be secreted and have important effects on the heart. Thus, in animal models of cardiomyopathy, pressure overload, and myocardial infarction, there are increases in both chymase mRNA levels and chymase activity in the heart. In human diseased heart homogenates, alterations in chymase activity have also been reported. These findings have raised the possibility that inhibition of chymase may have a role in the therapy of cardiac disease. The selective chymase inhibitors developed to date include TY-51076, SUN-C8257, BCEAB, NK320, and TEI-E548. These have yet to be tested in humans, but promising results have been obtained in animal models of myocardial infarction, cardiomyopathy, and tachycardia-induced heart failure. It seems likely that orally active inhibitors of chymase could have a place in the treatment of cardiac diseases where injury-induced mast cell degranulation contributes to the pathology.

Exploring the potential of xenobiotic-metabolising enzymes as biocatalysts: Evolving designer catalysts from polyfunctional cytochrome P450 enzymes

1. Biological catalysts have the advantage of being able to catalyse chemical reactions with an often exquisite degree of regio- and stereospecificity in contrast with traditional methods of organic synthesis. 2. The cytochrome P450 enzymes involved in human drug metabolism are ideal starting materials for the development of designer biocatalysts by virtue of their catalytic versatility and extreme substrate diversity. Applications can be envisaged in fine chemical synthesis, such as in the pharmaceutical industry and bioremediation. 3. A variety of techniques of enzyme engineering are currently being applied to P450 enzymes to explore their catalytic potential. Although most studies to date have been performed with bacterial P450s, reports are now emerging of work with mammalian forms of the enzymes. 4. The present minireview will explore the rationale and general techniques for redesigning P450s, review the results obtained to date with xenobiotic-metabolising forms and discuss strategies to overcome some of the logistic problems limiting the full exploitation of these enzymes as industrial-scale biocatalysts.

Potential of Sr isotopic analysis in ceramic provenance studies: Characterisation of Chinese stonewares

We compare the trace element and Sr isotopic compositions of stoneware bodies made in Yaozhou and Jizhou to characterise these Chinese archaeological ceramics and examine the potential of Sr isotopes in provenance studies. Element concentrations determined by ICP-MS achieve distinct characterisation for Jizhou samples due to their restricted variation, yet had limited success with Yaozhou wares because of their large variability. In contrast, Sr-87/Sr-86 ratios in Yaozhou samples have a very small variation and are all significantly lower than those of Jizhou samples, which show a large variation and cannot be well characterised with Sr isotopes. Geochemical interpretation reveals that Sr-87/Sr-86 ratios will have greater potential to characterise ceramics made of low Rb/Sr materials such as kaolin clay, yet will show larger variations in ceramics made of high Rb/Sr materials such as porcelain stone. (c) 2005 Elsevier B.V. All rights reserved.

Animal production potential of some new Leucaena accessions in the Markham valley, Papua New Guinea

Signal grass pastures were oversown with four Leucaena spp. planted in hedgerows and evaluated for their agronomic productivity and ability to support steer liveweight gains. Each Leucaena sp. (L. leucocephala, L. pallida, L colli. nst. i., L. trichandra) was planted as seedlings into two I ha paddocks in rows 5 m apart, with I m spacing between trees. Cattle were rotationally grazed on the 2 replicates of each species, as well as on two I ha paddocks of a signal grass on y (Brachiaria decumbens) control, over a 243-day period at a stocking rate of 3 steers/ha. Mean presentation yield and herbage allowance of the Leucaena accessions over the grazing period were highest for L pallida (1100 kg/ha and 0.8 kg DM/kg LW, respectively), followed by L. leucocephala (700 kg/ha and 0.5 kg DM/kg LW), L. collinsii (700 kg/ha and 0.4 kg DM/kg LW) and L. trichandra (300 kg/ha and 0.2 kg DM/kg LW). Despite only moderate presentation yields and herbage allowances, steers grazing L. leucocephala and L. collinsii accessions produced the highest mean liveweight gains (LWG) of 0. and 0.56 kg/hd/d, respectively. While L. pallida produced the highest DM yields, it supported the lowest LWG of 0.36 kg/hd/d. The mean LWGs of steers grazing L. trichandra and the control (grass only) treatments were similar at 0.48 kg/ hd/d. The possible reasons for the differences in steer performance on the different Leucaena accessions are discussed.

Determination of chromophore charge states in the low pH color transition of the fluorescent protein Rtms5(H146S) via time-dependent DFT

The red fluorescent protein Rtms5H146S displays a transition from blue (absorbance λmax 590 nm) to yellow (absorbance λmax not, vert, similar453 nm) upon titration to low pH. The pKa of the reaction depends on the concentration of halide, offering promise for new expressible halide sensors. The protonation state involved in the low pH form of the chromophore remains, however, ambiguous. We report calculated excitation energies of different protonation states of an RFP chromophore model. These suggest that the relevant titration site is the phenoxy moiety of the chromophore, and the relevant base and conjugate acid are anionic and neutral chromophore species, respectively.

Present and future potential of pineapple biotechnology

Pineapple is an important crop for many countries in Central and South America as well as the Asia-Pacific region. Even though the history of the crop dates to pre-Colombian times there is a remarkable lack of commercial varieties with a single cultivar ‘Smooth Cayenne’ dominating the whole industry. Variety improvement is a very difficult task for pineapple breeders and very little progress has been made in this respect when compared to other crops more suitable to classical breeding approaches. This special characteristic makes pineapple specially suited for genetic engineering approaches that can transfer specific traits from other species into pineapple. In this presentation past and present efforts to use biotechnological methods for the improvement of pineapple will be reviewed. On-going biotechnology projects include control of flowering and control of ‘blackheart’ disease. The development of pineapple biotechnology, as with any other crop, is dependent on the availability of a number of molecular tools, which will also be discussed. For pineapple, these tools can be roughly classified into three different categories: (1) availability of useful genes (2) availability of suitable promoters and (3) availability of an efficient transformation method.