How to use the paradigm of ischemic preconditioning to protect the heart?

Ischemic preconditioning affords the most powerful protection to a heart submitted to a prolonged ischemia-reperfusion. During the past decade, a huge amount of work allowed to better understand the features of this protective effect as well as the molecular mechanisms. Ischemic preconditioning reduces infarct size and improves functional recovery; its effects on arrhythmias remain debated. Triggering of the protection involves cell surface receptors that activate pro-survival pathways including protein kinase C, PI3-kinase, possibly Akt and ERK1/2, whose downstream targets remain to be determined. Much attention has been recently focused on the role of mitochondrial K(+)ATP channels and the permeability transition pore that seem to play a major role in the progression toward irreversible cellular injury. Based on these experimental studies attempts have been made to transfer preconditioning from bench to bedside. Human experimental models of ischemic preconditioning have been set up, including cardiac surgery, coronary angioplasty or treadmill exercise, to perform pathophysiological studies. Yet, protecting the heart of CAD (coronary artery disease) patients requires a pharmacological approach. The IONA trial has been an example of the clinical utility of preconditioning. It helped to demonstrate that chronic administration of nicorandil, a K(+)ATP opener that mimics ischemic preconditioning in experimental preparations, improves the cardiovascular prognosis in CAD patients. Recent experimental studies appear further encouraging. It appears that "postconditioning" the heart (i.e. performing brief episodes of ischemia-reperfusion at the time of reperfusion) is as protective as preconditioning. In other words, a therapeutic intervention performed as late as at the time of reflow can still significantly limit infarct size. Further work is needed to determine whether this may be transferred to the clinical practice.     

From Desirable Ornamental Plant to Pest to Accepted Addition to the Flora? – the Perception of an Alien Tree Species Through the Centuries

Prunus serotina, a forest tree of North American origin, was introduced to central Europe and planted for various purposes. In the course of the centuries it was regarded as a valuable timber tree by European foresters; subsequently, as a useful non-timber species in forestry, a forest pest, a controllable weed and, eventually, as a species we have to live with. All these perceived qualities served as motives for action by humans without seeking scientific evidence for them: millions of specimens of P. serotina were planted, later millions of euros were spent in attempts at control. The species, and its changing perception through time, may be an example of the need for science-based assessments as a basis for developing policies concerning non-native plants. This revised version was published online in July 2006 with corrections to the Cover Date.     

Stimulating the Need to Know…

Nations, James D. Tropical Rainforest: Endangered Environment . New York: Franklin Watts, 1988. 143 pp. $12.90 hardcover. Reviewed by Jorge Zamacona Evenes.

Sharp, D.W.A., ed. The Penguin Dictionary of Chemistry , 2d ed. New York: Penguin, 1990. 434 pp. $9.95 paperback. Reviewed by Wayne Hanley.

Hale, W.G., and J.P. Margham. The HarperCollins Dictionary of Biology. New York: Harper Collins, 1991. 569 pp. $12.95 paperback; $25.00 hardcover. Reviewed by Wayne Hanley.

Sparks, John, and Tony Soper. Penguins. New York: Fact On File, 1987. 246 pp. $1995 hardcover. Reviewed by Wayne Hanley.

Mountfort, Guy. Rare Birds of the World . A Collins/ICBP Handbook. New York: Penguin (The Stephen Greene Press), 1988. 256 pp. $2995 hardcover. Reviewed by John W. McLure.

Woodcock, Martin. Collins Handguide to the Birds of the Indian Subcontinent . New York: Penguin (The Stephen Greene Press), 1989. 176 pp. $11.95 paperback. Reviewed by James Scheib.

Harris, Michael. The Collins Field Guide to the Birds of Galapagos . New York: Penguin (The Stephen Greene Press), 1989. 160 pp. $1995 hardcover. Reviewed by Jim Fuller.

Brudenell-Bruce, P. G. C. The Collins Guide to the Birds of New Providence and the Babama Islands. New York: Penguin (The Stephen Greene Press), 1989. 142 pp. $14.95 paperback. Reviewed by Carol A. Thompson.     

Does the response of the intestinal epithelium to keratinocyte growth factor vary according to the method of administration?

BACKGROUND: Keratinocyte growth factor (KGF) is a potent mitogen and may be of value for the treatment of conditions such as short bowel syndrome and chemotherapy-induced mucositis. However the most efficacious route and method of administration is unclear. METHODS: Rats maintained by total parenteral nutrition (TPN) were given KGF (1 mg/kg/rat/day, i.v.) infused continuously or as a once-daily injection. The same dose was also given s.c. to chow-fed rats. Changes in gut growth were assessed by measurement of wet weight, proliferation (vincristine induced metaphase arrest) and crypt branching index. Changes in gut hormone profile were also determined to examine if any trophic effects were mediated via this mechanism. RESULTS: KGF caused a 70-100% increase in wet weight of the stomach, small and large intestine of TPN-fed rats (P < 0.01) with no significant differences seen between the two methods of administration. The increase in metaphase counts was greatest in the stomach (about seven-fold P < 0.01), but was less pronounced in the distal small intestine and colon (about 50% increase). The trophic effect of KGF was much less prominent in orally-fed rats. Crypt branching index was significantly reduced by KGF in the proximal small intestine of TPN, but not orally-fed rats. Plasma gastrin, PYY, total glucagon, enteroglucagon and GLP-1 all increased by two-three-fold (all P < 0.01) in response to KGF whereas insulin levels fell by about 25% in the TPN group. CONCLUSIONS: The mitogenic action of KGF occurred predominantly in the stomach and proximal small intestine. Its efficacy was less pronounced in orally-fed animals, suggesting KGF may be of greatest benefit in conditions associated with lowered intestinal proliferation. Clinical trials of KGF can probably use single daily i.v. injections without reduction in efficacy.     

How to Bring the “Unseen” Proteome to the Limelight via Electrophoretic Pre-Fractionation Techniques

The present review reports a panoply of electrophoretic methods as pre-fractionation tools in proteomic investigations in preparation for mass spectrometry or two-dimensional electrophoresis map analysis. Such electrophoretic pre-fractionation protocols include all those electrokinetic methodologies which are performed in free solution, most of them relying on isoelectric focusing steps (although some approaches based on gels and granulated media are also discussed). Devices associated with electrophoretic separations are multi-chamber apparatuses, such as the multi-compartment electrolyzers equipped with either isoelectric membranes or with isoelectric beads, Off-Gel electrophoresis in a multi-cup device and the Rotofor, an instrument also based on a multi-chamber system but exploiting the conventional technique of carrier-ampholyte-focusing. Other free-flow systems, as well as miniaturized chambers, are also described.     

Is Mislocalization during Saccades Related to the Position of the Saccade Target within the Image or to the Gaze Position at the End of the Saccade?

A stimulus that is flashed around the time of a saccade tends to be mislocalized in the direction of the saccade target. Our question is whether the mislocalization is related to the position of the saccade target within the image or to the gaze position at the end of the saccade. We separated the two with a visual illusion that influences the perceived distance to the target of the saccade and thus saccade endpoint without affecting the perceived position of the saccade target within the image. We asked participants to make horizontal saccades from the left to the right end of the shaft of a Müller-Lyer figure. Around the time of the saccade, we flashed a bar at one of five possible positions and asked participants to indicate its location by touching the screen. As expected, participants made shorter saccades along the fins-in (<–>) configuration than along the fins-out (>–<) configuration of the figure. The illusion also influenced the mislocalization pattern during saccades, with flashes presented with the fins-out configuration being perceived beyond flashes presented with the fins-in configuration. The difference between the patterns of mislocalization for bars flashed during the saccade for the two configurations corresponded quantitatively with a prediction based on compression towards the saccade endpoint considering the magnitude of the effect of the illusion on saccade amplitude. We conclude that mislocalization is related to the eye position at the end of the saccade, rather than to the position of the saccade target within the image.     

From the Zulu medicine to the European phytomedicine Umckaloabo®

Among the Zulus of South Africa a crude root drug of initially unknown botanical origin was used for the treatment of pulmonary diseases and tuberculosis (TB). An English TB patient called “Stevens” heard about it and travelled to South Africa where, according to his account, he was cured by taking an extract of the crude drug. It was extremely difficult to establish the imported crude herbal drug as a “new TB medicine”, as neither the plant from which the drug originated was identified nor were the constituents and pharmacological effects known at that time.It was only after a professional search and initial chemical and taxonomic investigations enabled the identity of the plant to be determined that the requirements were met for comprehensive chemical, pharmacological and clinical research into the crude drug.The following report traces the long and difficult path of this “mystery drug” from the Zululand of South Africa to the laboratories of Europe.     

Is ligation the only solution to the pyrophosphate problem?

Pyrophosphate linkages are easily formed during the nonenzymatic oligomerization of activated nucleotides. They often form caps which terminate an oligonucleotide with a 5-5 pyrophosphate. Owing to their structural resemblance to the intermediates in enzymatic ligation reactions, it has been suggested that pyrophosphate caps might have been capable of acting as activating groups in chain elongation processes. We argue that an alternative possibility would have been the specific hydrolysis of pyrophosphates.     

Does the reticular thalamic nucleus project to the midbrain?

In this study, we investigated whether the reticular thalamic nucleus has a projection to major centres of the midbrain in rats, rabbits and cats. Various tracers (biotinylated dextran, cholera toxin B subunit, fluorescent latex beads) were injected either into the midbrain tectum (deep layers of the superior colliculus) or tegmentum (midbrain reticular and pedunculopontine nuclei). In other experiments, different coloured latex beads (red and green) were injected into the deep layers of the superior colliculus and into the midbrain reticular nucleus of the same animal (rabbits). Our major finding is that in rats, rabbits and cats, there are no retrogradely labelled cells in the reticular thalamic nucleus after tracer injections into the abovementioned midbrain centres. In rabbits and cats, however, there are retrogradely labelled cells lying close to the ventromedial edge of the reticular thalamic nucleus after such injections. We show, by means of immunocytochemical double-labelling, that these retrogradely labelled cells do not lie in the reticular thalamic nucleus as suggested by previous studies, but in the inner small-celled region, a group of small cells that forms part of the zona incerta. Although there appears to be no clear topography of projection of the inner small-celled region, our tracer double-labelling experiments show that separate cells in the inner small-celled region project to individual centres of the midbrain (i.e., there are very few double-labelled cells after double injections). In rats, unlike in rabbits and cats, there is no clearly defined inner small-celled region and there are no retrogradely labelled cells seen along the ventromedial edge of the reticular thalamic nucleus. Our results suggest that in rats, rabbits and cats, there is no projection of the reticular thalamic nucleus to major centres of the midbrain, suggesting that the nucleus may not have a very strong influence on midbrain function, as it does on dorsal thalamic function.     

Dissecting the molecular damage to stallion spermatozoa: the way to improve current cryopreservation protocols?

We review recent developments in the technology of freezing stallion sperm, paying special attention to the molecular lesions that spermatozoa suffer during freezing and thawing, such as osmotic stress, oxidative damage, and apoptotic changes. We also discuss the applicability of colloidal centrifugation in stallion sperm cryobiology. Increased knowledge about the molecular injuries that occur during cryopreservation may lead to improved protective techniques and thus to further improvements in fertility in the current decade.     

Immunity to helminths: Ready to tip the biochemical balance?

Using data from recent laboratory and field studies, Peter Brophy and David Pritchard here summarize our current understanding of the approximate sequence of events leading to protective immune responses against some chronic parasitic helminth infections.     

How to determine the susceptibility of Meligethes aeneus to neonicotinoids?

Three different bioassays were used to determine the susceptibility to the neonicotinoid Biscaya^® of oilseed rape pollen beetles collected from fields in Bavaria. The one in which the test substance was applied to the inner wall of glass tubes is recommended for future studies on pollen beetles because it is not dependent on the availability of plant material and provides precise information on the amount of insecticide required per unit area.     

UN system efforts to support the response to AIDS in China

INTRODUCTION China has made considerable progress in the response to the AIDS epidemic in the past years, particularly in terms of commitment by the national leadership, the establish- ment of a supportive policy framework, improved under- standing of the…