The use of adjunctive GPIIb/IIIa inhibitors in patients with unstable angina/non-Q-wave MI undergoing percutaneous coronary intervention

Glycoprotein IIb/IIIa receptor inhibitors represent a relatively new therapeutic approach in the field of antiplatelet therapy. Following the development of abciximab a number of small molecule GPIIb/IIIa inhibitors have been introduced such as tirofiban and eptifibatide. In this fast-moving field the interventional cardiologist needs a framework to guide decision-making for the individual patient. This review covers the efficacy and safety data from the clinical trials of GPIIb/IIIa inhibitors in the context of patients undergoing percutaneous coronary intervention for unstable angina/non-Q-wave myocardial infarction. There is an increasing body of evidence to support the efficacy of GPIIb/IIIa inhibitors in reducing the risk of adverse ischemic events in high and low risk patients undergoing percutaneous coronary intervention. A number of unresolved efficacy and safety issues remain, including the duration of treatment before and after intervention; whether a reduction in the heparin dose would further decrease the risk of hemorrhage without affecting the periprocedural thrombotic rate in patients undergoing PTCA with adjunctive GPIIb/IIIa inhibitors; and the cost-effectiveness of this therapy. When a thorough analysis of cost-effectiveness has been made, it will be easier to advocate the widespread use of these agents in all patients undergoing coronary intervention.     

Comparison of glyoxalase I purified from yeast (Saccharomyces cerevisiae) with the enzyme from mammalian sources

Glyoxalase I from yeast (Saccharomyces cerevisiae) purified by affinity chromatography on S-hexylglutathione-Sepharose 6B was characterized and compared with the enzyme from rat liver, pig erythrocytes and human erythrocytes. The molecular weight of glyoxalase I from yeast was, like the enzyme from Rhodospirillum rubrum and Escherichia coli, significantly less (approx. 32000) than that of the enzyme from mammals (approx. 46000). The yeast enzyme is a monomer, whereas the mammalian enzymes are composed of two very similar or identical subunits. The enzymes contain 1Zn atom per subunit. The isoelectric points (at 4 degrees C) for the yeast and mammalian enzymes are at pH7.0 and 4.8 respectively; tryptic-peptide ;maps' display corresponding dissimilarities in structure. These and some additional data indicate that the microbial and the mammalian enzymes may have separate evolutionary origins. The similarities demonstrated in mechanistic and kinetic properties, on the other hand, indicate convergent evolution. The k(cat.) and K(m) values for the yeast enzyme were both higher than those for the enzyme from the mammalian sources with the hemimercaptal adduct of methylglyoxal or phenylglyoxal as the varied substrate and free glutathione at a constant and physiological concentration (2mm). Glyoxalase I from all sources investigated had a k(cat.)/K(m) value near 10(7)s(-1).m(-1), which is close to the theoretical diffusion-controlled rate of enzyme-substrate association. The initial-velocity data show non-Michaelian rate saturation and apparent non-linear inhibition by free glutathione for both yeast and mammalian enzyme. This rate behaviour may have physiological importance, since it counteracts the effects of fluctuations in total glutathione concentrations on the glyoxalase I-dependent metabolism of 2-oxoaldehydes.     

On the Development of the Eminentia Mediana of the Hypophysis in Rana temporaria, Studied in Normal, Hypophysectomized, and Thyroidectomized Tadpoles.

In the Rana temporaria tadpole, the part of the infundibular floor that eventually becomes the eminentia mediana is very thin throughout premetamorphosis; the supply of aminergic and neurosecretory nerves is poor, and the area is covered by a few fenestrated capillaries. The organ begins to thicken around mid-prometamorphosis owing to a marked invasion of nerves. At this stage it is also penetrated by capillaries and perivascular space extensions, which together form the neurovascular link structures. These become more pronounced during metamorphic climax, when the eminentia mediana attains the adult appearance. Development of the organ is arrested at the premetamorphic stage after thyroidectomy in the young premetamorphic tadpole. Removal of the adenohypophysial primordium from the embryo of the tailbud stage prevents the vascular—but not the neural—component of the eminentia from developing beyond the premetamorphic stage. By contrast, in the American Rana -species investigated the neural component also fails to develop after hypophysectomy.     

Local Knowledge and Conservation of Seagrasses in the Tamil Nadu State of India

Local knowledge systems are not considered in the conservation of fragile seagrass marine ecosystems. In fact, little is known about the utility of seagrasses in local coastal communities. This is intriguing given that some local communities rely on seagrasses to sustain their livelihoods and have relocated their villages to areas with a rich diversity and abundance of seagrasses. The purpose of this study is to assist in conservation efforts regarding seagrasses through identifying Traditional Ecological Knowledge (TEK) from local knowledge systems of seagrasses from 40 coastal communities along the eastern coast of India. We explore the assemblage of scientific and local traditional knowledge concerning the 1. classification of seagrasses (comparing scientific and traditional classification systems), 2. utility of seagrasses, 3. Traditional Ecological Knowledge (TEK) of seagrasses, and 4. current conservation efforts for seagrass ecosystems. Our results indicate that local knowledge systems consist of a complex classification of seagrass diversity that considers the role of seagrasses in the marine ecosystem. This fine-scaled ethno-classification gives rise to five times the number of taxa (10 species = 50 local ethnotaxa), each with a unique role in the ecosystem and utility within coastal communities, including the use of seagrasses for medicine (e.g., treatment of heart conditions, seasickness, etc.), food (nutritious seeds), fertilizer (nutrient rich biomass) and livestock feed (goats and sheep). Local communities are concerned about the loss of seagrass diversity and have considerable local knowledge that is valuable for conservation and restoration plans. This study serves as a case study example of the depth and breadth of local knowledge systems for a particular ecosystem that is in peril.     

Quantitative Analysis of the Chloroplast Molecular Chaperone ClpC/Hsp93 in Arabidopsis Reveals New Insights into Its Localization,Interaction with the Clp Proteolytic Core,and Functional Importance

The molecular chaperone ClpC/Hsp93 is essential for chloroplast function in vascular plants. ClpC has long been held to act both independently and as the regulatory partner for the ATP-dependent Clp protease, and yet this and many other important characteristics remain unclear. In this study, we reveal that of the two near-identical ClpC paralogs (ClpC1 and ClpC2) in Arabidopsis chloroplasts, along with the closely related ClpD, it is ClpC1 that is the most abundant throughout leaf maturation. An unexpectedly large proportion of both chloroplast ClpC proteins (30% of total ClpC content) associates to envelope membranes in addition to their stromal localization. The Clp proteolytic core is also bound to envelope membranes, the amount of which is sufficient to bind to all the similarly localized ClpC. The role of such an envelope membrane Clp protease remains unclear although it appears uninvolved in preprotein processing or Tic subunit protein turnover. Within the stroma, the amount of oligomeric ClpC protein is less than that of the Clp proteolytic core, suggesting most if not all stromal ClpC functions as part of the Clp protease; a proposal supported by the near abolition of Clp degradation activity in the clpC1 knock-out mutant. Overall, ClpC appears to function primarily within the Clp protease, as the principle stromal protease responsible for maintaining homeostasis, and also on the envelope membrane where it possibly confers a novel protein quality control mechanism for chloroplast preprotein import.     

Applications of mineral nutrients to heavily N-fertilized Scots pine trees: Effects on arginine and mineral nutrient concentrations

The aim of the investigation was to study if improved nutrient status in Scots pine (Pinus sylvestris L) trees would be reflected in decreased concentrations of arginine in the needles. The studies trees had imbalanced mineral nutrient composition and elevated needle arginine concentrations caused by long-term fertilization with N. Concentrations of arginine and mineral nutrients in needles were followed over three consecutive years of additional fertilization with N alone or with P, K, Mg and micronutrients in combination with and without N.Analysis of needle mineral concentrations suggested that there were deficiencies only in K and Mg. The N concentration increased both in trees fertilized with N alone and in trees fertilized with N in combination with mineral nutrients. In the control treatment and in trees fertilized with mineral nutrients other than N the N concentration remained fairly constant. The highest Ca/N, K/N and P/N ratios were found in trees fertilized with mineral nutrients other than N while the lowest ratios were found in trees fertilized with N alone. Arginine concentrations in needles from trees fertilized with N alone remained at a high level throughout the experiment while arginine concentrations in trees given the other treatments decreased.The results show that the mineral nutrient balance can be improved with appropriate fertilization and that this improvement is reflected in decreasing arginine levels. Furthermore the study demonstrates that when N supply is reduced the arginine concentration also decreases also as an effect of reduced N supply per se. The study also indicates that arginine may be a better measure of the N status in pine trees than total N.     

Genes co-expressed with CPSAR1 identified using ATTED-II

Identification of interacting proteins will help to investigate further the relationship between CPSAR1 and the vesicle transport system or the ribosomes. Thus, we adopted a bioinformatic approach, using the publicly available Arabidopsis thaliana trans-factor and cis-element prediction database, ATTED-II (http://atted.jp/), to identify putative protein interactors. The proteins directly linked to CPSAR1 were almost exclusively nucleus encoded and several were involved in protein synthesis of which three were thylakoid localized. The list of putative interacting proteins does not exclude any of the previous proposed actions of CPSAR1 but encourage more detailed examination of the role of CPSAR1.Key words: Arabidopsis, chloroplast, co-expression, protein cargo, vesicle transportChloroplast protein targeting has been intensively studied.^1–4 Transport of non-proteinaceous material, such as lipids, to the thylakoid has not been studied to the same extent, although several reports do exist.^5–8 Since thylakoids do not produce lipids themselves any lipids present must have been transported from the production site, i.e., the envelope.^9,10 Experimental data support the theory of a vesicular transport system and it has been predicted that several proteins resembling those important in the cytosolic vesicle transport system are chloroplast localized.¹¹ Recently we confirmed that one of these proteins, CPSAR1, is located in the chloroplast and has features similar to the cytosolic COPII-related Sar1 protein, i.e., it is found at the donor membrane and in the vesicle, but not at the acceptor membrane. In addition, other research groups^12,13 have also found that CPSAR1 is chloroplast localized but refer to it as atOBGL or atObgM, respectively, since CPSAR1 shares high sequence similarity with proteins belonging to the Obg-family. The roles of Obg proteins are very diverse, but a role closely connected to ribosomes has been suggested for CPSAR1.¹² CPSAR1 being part of a vesicle system does not exclude it from having a role in relation to ribosomes. The existence of a coiled-coil motif and a GTP binding domain, in combination with the suggested role as part of a vesicle transport system, makes it a highly attractive idea that CPSAR1 interacts with other proteins.