Does 'imprinting' with low prenatal vitamin D contribute to the risk of various adult disorders?

Hypovitaminosis D is a candidate risk-modifying factor for a diverse range of disorders apart from rickets and osteoporosis. Based on epidemiology, and on in vitro and animal experiment, vitamin D has been linked to multiple sclerosis, certain cancers (prostate, breast and colorectal), insulin-dependent diabetes mellitus and schizophrenia. I hypothesise that low pre- and perinatal vitamin D levels imprint on the functional characteristics of various tissues throughout the body, leaving the affected individual at increased risk of developing a range of adult-onset disorders. The hypothesis draws from recent advances in our understanding of the early origin of adult disease and proposes a 'critical window' during which vitamin D levels may have a persisting impact on adult health outcomes. Methods to test the hypothesis are outlined. If correct, the hypothesis has important implications for public health. Careful attention to maternal vitamin D status could translate into diverse improvements in health outcomes for the following generation. (C) 2001 Harcourt Publishers Ltd.

Skeletal effects of low-intensity pulsed ultrasound on the ovariectomized rodent

Growing evidence supports low-intensity pulsed ultrasound (US) as an osteogenic mechanical stimulus. Its effects on isolated bone cells and on fractured bone are established. However, its effects on osteoporosis are not clear. This study examined US effects on ovariectomy (OVX) induced bone changes within the rodent hindlimb (distal femur and proximal tibia), and on normal bone in animals following sham-OVX. Animals were exposed to daily unilateral active-US and contralateral inactive-US for 12 weeks. Bone status was assessed using dual energy X-ray absorptiometry and histomorphometry. Ovariectomy resulted in significant bone changes. Low-intensity pulsed US did not influence these changes. These results suggest that the US dose introduced may not be a beneficial treatment for osteoporosis, and that intact bone may be less sensitive to US than fractured bone and isolated bone cells. This may relate to the biophysical mechanisms of action of US, US-bone interactions and tissue level processes taking place.

The effect of heat treatment on the toughness, hardness and microstructure of low carbon white cast irons

The effect of destabilisation and subcritical heat treatment on the impact toughness, hardness, and the amount and mechanical stability of retained austenite in a low carbon white cast iron have been investigated. The experimental results show that the impact energy constantly increases when the destabilisation temperature is raised from 950 degreesC to 1200 degreesC. Although the hardness decreases, the heat-treated hardness is still greater than the as-cast state. After destabilisation treatment at 1130 degreesC, tempering at 200 to 250 degreesC for 3 hours leads to the highest impact toughness, and secondary hardening was observed when tempering over 400 degreesC. The amount of retained austenite increased with the increase in the destabilisation temperature, and the treatment significantly improves the mechanical stability of the retained austenite compared with the as-cast state. Tempering below 400 degreesC does not affect the amount of retained austenite and its mechanical stability. But the amount of retained austenite is dramatically reduced when tempered above 400 degreesC. The relationship between the mechanical properties and the microstructure changes was discussed. (C) 2001 Kluwer Academic Publishers.

Surgical outcomes of a randomized prospective trial involving patients with a proximal femoral fracture

Background: An orthopaedic management/patient-focused care unit (OMPFCU) involving a dedicated orthopaedic-geriatrics liaison team was established at the Royal Brisbane Hospital in 1994 in an effort to safely accelerate rehabilitation of patients with proximal femoral fractures. Methods: The surgical outcomes of the patients were monitored in order to determine whether accelerated rehabilitation had any significant adverse effects on the surgical outcomes, measured by mortality, readmission to hospital, deep wound infection, fracture union delay, mobility and the revision surgery rate. Results: No significant difference was recorded in mortality and morbidity, deep wound infection and revision surgery rates between patients in the Royal Brisbane Hospital OMPFCU and those in standard care in the orthopaedic surgery wards. Conclusion: Accelerated rehabilitation for patients with a proximal femoral fracture in a major teaching hospital can be accomplished safely.

Familial Paget's disease of bone: Nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree

Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q121.1-q22 (PDB2) in different pedigrees, We have identified a large pedigree of over 250 individuals with 49 informative individuals affected with Paget's disease of bone; 31 of whom are available for genotypic analysis. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Linkage analysis has been performed with markers at PDB1; these data show significant exclusion of linkage with log,, of the odds ratio (LOD) scores < -2 in this region. Linkage analysis of microsatellite markers from the PDB2 region has excluded linkage with this region, with a 30 cM exclusion region (LOD score < -2.0) centered on D18S42, These data confirm the genetic heterogeneity of Paget's disease of bone. Our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning.

Reinfection with Schistosoma haematobium following school-based chemotherapy with praziquantel in four highly endemic villages in Côte d'Ivoire

We present the comparative evaluation of school-based chemotherapy with praziquantel on Schistosoma haematobium reinfection patterns, 6, 12, 18 and 24 months after systematic treatment of schoolchildren in four villages of south-central Côte d'Ivoire. At baseline, very high S. haematobium infection prevalences of 88–94% were found in Taabo Village, located adjacent to a large man-made lake, and in Batera and Bodo, where small dams were constructed. In Assinzé, a village with no man-made environmental alterations, the baseline infection prevalence was significantly lower (67%). The parasitological cure rate, assessed 4 weeks after praziquantel administration in the village with the highest prevalence and intensity of infection, was high (82%), and showed a clear association with infection intensity prior to treatment. Six months after chemotherapy, significant reductions in the prevalence and intensity of infection were observed in all villages. However, infection prevalence was again high in Taabo Village (63%) and in Batera (49%). Different patterns of reinfection occurred in the four villages: rapid reinfection in Taabo Village to reach almost baseline infection prevalence 12 months post-treatment; slow but gradual increase in the prevalence and intensity of infection in Bodo; marked increase in prevalence and intensity of infection during the second year of the follow-up in Assinzé; and prevalence and intensity of infection that remained almost constant between 6 and 24 months post-treatment in Batera. Our study confirms that S. haematobium reinfection patterns largely depend on the local epidemiological setting, which is of central importance to tailoring treatment strategies that are well adapted to these different settings.

Cleavage of hemoglobin by hookworm cathespin D aspartic proteases and its potential contribution to host specificity

Hookworms routinely reach the gut of nonpermissive hosts but fail to successfully feed, develop, and reproduce. To investigate the effects of host-parasite coevolution on the ability of hookworms to feed in nonpermissive hosts, we cloned and expressed aspartic proteases from canine and human hookworms. We show here that a cathepsin D-like protease from the canine hookworm Ancylosotoma caninum (Ac-APR-1) and the orthologous protease from the human hookworm Necator americanus (Na-APR-1) are expressed in the gut and probably exert their proteolytic activity extracellularly. Both proteases were detected immunologically and enzymatically in somatic extracts of adult worms. The two proteases were expressed in baculovirus, and both cleaved human and dog hemoglobin (Hb) in vitro. Each protease digested Hb from its permissive host between twofold (whole molecule) and sixfold (synthetic peptides) more efficiently than Hb from the nonpermissive host, despite the two proteases' having identical residues lining their active site clefts. Furthermore, both proteases cleaved Hb at numerous distinct sites and showed different substrate preferences. The findings suggest that the paradigm of matching the molecular structure of the food source within a host to the molecular structure of the catabolic proteases of the parasite is an important contributing factor for host-parasite compatibility and host species range.

Total synthesis and absolute stereochemistry of plakortone D

The first total synthesis of plakortone D is described and thereby establishes the structure and absolute stereochemistry of the most biologically active member of the marine-derived plakortone family. The sterically congested bicyclic lactone core results from a Pd(II)-induced hydroxycyclization−carbonylation−lactonization sequence on an enediol whose chirality was installed by AD-technology. Attachment of the side chain, also constructed using AD-methodology, was achieved by using a modified Julia coupling. The described approach enables acquisition of other plakortones and analogues, in the correct (natural) stereochemical series.