Do physicians have an ethical obligation to care for patients with AIDS?

This paper responds to the question: Do physicians have an ethical obligation to care for patients with acquired immunodeficiency syndrome (AIDS)? First, the social and political milieu in which this question arises is sampled. Here physicians as well as other members of the community are found declaring an unwillingness to be exposed to people with AIDS. Next, laws, regulations, ethical codes and principles, and the history of the practice of medicine are examined, and the literature as it pertains to these areas is reviewed. The obligation to care for patients with AIDS, however, cannot be located in an orientation to morality defined in rules and codes and an appeal to legalistic fairness. By turning to the orientation to morality that emerges naturally from connection and is defined in caring, the physicians'' ethical obligation to care for patients with AIDS is found. Through an exploration of the writings of modern medical ethicists, it is clear that the purpose of the practice of medicine is healing, which can only be accomplished in relationship to the patient. It is in relationship to patients that the physician has the opportunity for self-realization. In fact, the physician is physician in relationship to patients and only to the extent that he or she acts virtuously by being morally responsible for and to those patients. Not to do so diminishes the physician''s ethical ideal, a vision of the physician as good physician, which has consequences for the physician''s capacity to care and for the practice of medicine.     

Amyloid excess in Alzheimer's disease: what is cholesterol to be blamed for?

A link between alterations in cholesterol homeostasis and Alzheimer's disease (AD) is nowadays widely accepted. However, the molecular mechanism/s underlying such link remain unclear. Numerous experimental evidences support the view that changes in neuronal membrane cholesterol levels and/or subcellular distribution determine the aberrant accumulation of the amyloid peptide in the disease. Still, this view comes from rather contradictory data supporting the existence of either high or low brain cholesterol content. This is of particular concern considering that therapeutical strategies aimed to reduce cholesterol levels are already being tested in humans. Here, we review the molecular mechanisms proposed and discuss the perspectives they open.     

Maintainence of parasitaemia - is it to die for?

One of the major differences between protozoan differentiation and metazoan differentiation is that protozoan cells normally retain potency during differentiation, which need not, therefore, be considered altruistic. Altruism does, however, arise at the level of the organism and consequently, protozoons have the potential to evolve altruistic traits. This is particularly true when, as with Trypanosoma brucei parasitaemias, populations are genetically homogeneous. This essay argues that whilst reports of altruistic phenomena during the trypanosome life cycle remain controversial, the prospect of reagents able to instigate pathways of cell death or differentiation bears further investigation.     

Carbohydrates: is the advice to eat less justified for diabetes and cardiovascular health?

PURPOSE OF REVIEW: Recent randomized controlled trials examining diets of varying carbohydrate composition recommended for people with diabetes and cardiovascular disease and those at risk are summarized. RECENT FINDINGS: Severe carbohydrate restriction results in appreciable initial weight loss and improvement in risk factors. After a year, however, the beneficial effects are equal to or less than those achieved on conventional alternatives. Some people develop elevations of LDL cholesterol. Modest carbohydrate restriction with relatively high intakes of cis-unsaturated fatty acids and protein is acceptable to many people and is more likely to produce sustained benefit in terms of weight loss and cardiovascular risk indicators. SUMMARY: Diets involving moderate carbohydrate restriction are suitable alternatives to high-carbohydrate, high-fibre diets for weight loss and reduction of cardiovascular disease and diabetes risk, as well as to treat individuals with the conditions. As such diets are generally high in protein and unsaturated fatty acids, they are not recommended for those with established or incipient nephropathy. High-carbohydrate, high-fibre diets remain appropriate for use in all those situations, provided carbohydrate is derived principally from minimally processed wholegrain breads and cereals and intact vegetables and fruit. Lower carbohydrate options may be preferable for markedly insulin-resistant individuals.     

Vibrio cholerae hemolysin: The β-trefoil domain is required for folding to the native conformation

Vibrio cholerae cytolysin/hemolysin (VCC) is a 65 kDa β-pore-forming toxin causing lysis and death of eukaryotic cells. Apart from the core cytolysin domain, VCC has two lectin domains with β-trefoil and β-prism folds. The β-prism domain binds to cell surface carbohydrate receptors; the role of the β-trefoil domain is unknown. Here, we show that the pro-VCC mutant without the β-trefoil domain formed aggregates highly susceptible to proteolysis, suggesting lack of a properly folded compact structure. The VCC variants with Trp532Ala or Trp534Ala mutation in the β-trefoil domain formed hemolytically inactive, protease-resistant, ring-shaped SDS-labile oligomers with diameters of ~19 nm. The Trp mutation induced a dramatic change in the global conformation of VCC, as indicated by: (a) the change in surface polarity from hydrophobic to hydrophilic; (b) movement of core Trp residues to the protein-water interface; and (c) decrease in reactivity to the anti-VCC antibody by >100-fold. In fact, the mutant VCC had little similarity to the wild toxin. However, the association constant for the carbohydrate-dependent interaction mediated by the β-prism domain decreased marginally from ~3×10⁸ to ~5×10⁷ M^?1. We interpret the observations by proposing: (a) the β-trefoil domain is critical to the folding of the cytolysin domain to its active conformation; (b) the β-prism domain is an autonomous folding unit.     

Postural preparation to making a step: is there a 'motor program' for postural preparation?

We tested the hypothesis that a sequence of mechanical events occurs preceding a step that scales in time and magnitude as a whole in a task-specific manner, and is a reflection of a "motor program." Young subjects made a step under three speed instructions and four tasks: stepping straight ahead, down a stair, up a stair, and over an obstacle. Larger center-of-pressure (COP) and force adjustments in the anterior-posterior direction and smaller COP and force adjustments in the mediolateral direction were seen during stepping forward and down a stair, as compared with the tasks of stepping up a stair and over an obstacle. These differences were accentuated during stepping under the simple reaction time instruction. These results speak against the hypothesis of a single motor program that would underlie postural preparation to stepping. They are more compatible with the reference configuration hypothesis of whole-body actions.     

Is it ethical for patients with renal disease to purchase kidneys from the world's poor?

BACKGROUND TO THE DEBATE: In many countries, the number of patients waiting for a kidney transplant is increasing. But there is a widespread and serious shortage of kidneys for transplantation, a shortage that can lead to suffering and death. One approach to tackling the shortage is for a patient with renal disease to buy a kidney from a living donor, who is often in a developing country, a sale that could--in theory at least--help to lift the donor out of poverty. Such kidney sales are almost universally illegal. Proponents of kidney sales argue that since the practice is widespread, it would be safer to formally regulate it, and that society should respect people's autonomous control over their bodies. Critics express concern about the potential for exploitation and coercion of the poor, and about the psychological and physical after-effects on the donors of this illegal kidney trade.     

Abandoned Foreigners: is the stage set for exotic pet reptiles to invade Central Europe?

Considerable scientific, politic and economic attention has been directed to biological invasions. Multiple pathways serve to introduce species to new environments and the release or escape of pets are among the most important sources for species invasions. Risk assessments help to identify species that are likely to become invasive and to set up preventive measures. Weighing the relative importance of ecological and human factors driving the establishment success of abandoned pets, we here present a new methodological guideline to help prioritising management activities for frequently traded pet reptiles. Climate match scores between the different distribution ranges as well as traits and niche axes shared by native and non-native species were assessed. Moreover, we tested for discrepancies in niche breadth between native and non-native ranges and estimated the ability of species to coexist with humans. Potentially moderate to high establishment success in most species was linked to appropriate climate match scores, broader niches with restrained human impacts and high similarities in reproductive traits with the native herpetofauna. Providing baseline information on the invasion potential of pet reptiles, this assessment calls for trade regulations and, to an even greater degree, for large scale education campaigns to prevent the establishment of non-native populations.     

Knowledgebase for addiction-related genes: is it possible an extrapolation to rational multi-target drug design?

In recent years the single-probe-single-target approach in drug design has started to be smoothly replaced by the single-probe-multiple-target (or multi-target) one, where a single drug is able to tackle different, but disease-related targets in a selective manner. However, the design of multi-target drugs has been hindered by a lack of a systematic network of disease-related common pathways. The recent development of the knowledgebase of addiction-related genes (KARG) has provided important hints on how to rationally design multi-target probes by connecting experimental techniques with available network models. In this perspective, the use of KARG as a template to build knowledgebases of disease-related genes for the rational multi-target drug design is suggested. Moreover, it is proposed that building knowledgebases of disease-related genes will become a necessary and ubiquitous tool in the rational design of multi-target drugs.