The unusual kinetics of lactate dehydrogenase of Schistosoma mansoni and their role in the rapid metabolic switch after penetration of the mammalian host.

Lactate dehydrogenase (LDH) from Schistosoma mansoni has peculiar properties for a eukaryotic LDH. Schistosomal LDH (SmLDH) isolated from schistosomes, and the recombinantly expressed protein, are strongly inhibited by ATP, which is neutralized by fructose-1,6-bisphosphate (FBP). In the conserved FBP/anion binding site we identified two residues in SmLDH (Val187 and Tyr190) that differ from the conserved residues in LDHs of other eukaryotes, but are identical to conserved residues in FBP-sensitive prokaryotic LDHs. Three-dimensional (3D) models were generated to compare the structure of SmLDH with other LDHs. These models indicated that residues Val187, and especially Tyr190, play a crucial role in the interaction of FBP with the anion pocket of SmLDH. These 3D models of SmLDH are also consistent with a competitive model of SmLDH inhibition in which ATP (inhibitor) and FBP (activator) compete for binding in a well-defined anion pocket. The model of bound ATP predicts a distortion of the nearby key catalytic residue His195, resulting in enzyme inhibition. To investigate a possible physiological role of this allosteric regulation of LDH in schistosomes we made a kinetic model in which the allosteric regulation of the glycolytic enzymes can be varied. The model showed that inhibition of LDH by ATP prevents fermentation to lactate in the free-living stages in water and ensures complete oxidation via the Krebs cycle of the endogenous glycogen reserves. This mechanism of allosteric inhibition by ATP prevents the untimely depletion of these glycogen reserves, the only fuel of the free-living cercariae. Neutralization by FBP of this ATP inhibition of LDH prevents accumulation of glycolytic intermediates when S. mansoni schistosomula are confronted with the sudden large increase in glucose availability upon penetration of the final host. It appears that the LDH of S. mansoni is special and well suited to deal with the variations in glucose availability the parasite encounters during its life cycle.

A review of the global literature on dental therapists.

OBJECTIVE: Access to adequate oral health care is deficient in many parts of the world. Many countries are now using dental therapists to increase access, particularly for children. To inform the discussion on dental therapists in the workforce, particularly in the United States, the W.K. Kellogg Foundation funded a review of the global literature to identify as many documents as possible related to the practice of dental therapists since the establishment of the School Dental Service in New Zealand in 1921. METHODS: Consultants in each of the countries considered to have a substantive literature on dental therapists were asked to participate in the research; seventeen in total. In addition to identifying and reviewing published articles, a focus of the research was on identifying 'gray' documents. Standard databases were searched for key words associated with dental therapists. In addition, searches were conducted of the governmental and dental association websites of all countries known to have dental therapists in their oral health workforce. RESULTS: Fifty-four countries, both developing and developed, were identified where dental therapists are members of the workforce. Eleven hundred documents were identified from 26 of these countries, with over 2/3 of them cited in the published monograph. Reliable evidence from the related literature and verbal communication confirmed the utilization of dental therapists in an additional 28 countries. Thirty-three of the countries were members of the Commonwealth of Nations, suggesting a mechanism of spread from New Zealand. Variable lengths of training/education existed for dental therapists with the tradition being 2 years postsecondary. In a few countries, the training of therapists and hygienists is now being combined in a three academic year program. Historically, dental therapists have been employed by government agencies caring for children, typically in school-based programs. Initiatives in some countries allow limited care for adults by dental therapists with additional training. CONCLUSIONS: The evidence indicates that dental therapists provide effective, quality, and safe care for children in an economical manner and are generally accepted both by the public and where their use is established, by the dental profession.

More attention to public health in the European Union - implications for dentistry?

At present the European Union is developing its competence on health and new important issues will be taken on board in European health policy. Increasing mobility of people and integration of the applicant countries puts pressure on the current health care provision systems. A mandate for an open co-ordination process in public health is expected to be given by the European Council. The process will start by exchange of information and best practice models. The next step will be the presentation of common targets between member countries, followed by national action programmes and indicators. It is likely that a lot of emphasis will be put on access to health services, comparisons of costs of health care and benchmarking the costs of items of care. In the long run this will mean convergence of the health care systems. If oral health is to be considered an integral part of general health dental professionals need to be aware of and be able to influence the actions to be taken.