Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys

Retention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate (CaOx) crystal binding during wound healing. This concept was investigated in vivo by treating rats for 1, 4, and 8 d with ethylene glycol (0.5 and 0.75%) in their drinking water to induce renal tubular cell damage and CaOx crystalluria. Tubular injury was morphologically scored on periodic acid-Schiff-stained renal tissue sections and tissue repair assessed by immunohistochemical staining for proliferating cell nuclear antigen. CaOx crystals were visualized in periodic acid-Schiff-stained sections by polarized light microscopy, and renal calcium deposits were quantified with von Kossa staining. HA was visualized with HA-binding protein and OPN and CD44 immunohistochemically with specific antibodies and quantified with an image analyzer system. Already after 1 d of treatment, both concentrations of ethylene glycol induced hyperoxaluria and CaOx crystalluria. At this point, there was neither tubular injury nor crystal retention in the kidney, and expression of HA, OPN, and CD44 was comparable to untreated controls. After 4 and 8 d of ethylene glycol, however, intratubular crystals were found adhered to injured/regenerating (proliferating cell nuclear antigen positive) tubular epithelial cells, expressing HA, OPN, and CD44 at their luminal membrane. In conclusion, the expression of HA, OPN, and CD44 by injured/regenerating tubular cells seems to play a role in retention of crystals in the rat kidney

Increased serum strontium levels in dialysis patients: An epidemiological survey

Increased serum strontium levels in dialysis patients: An epidemiological survey.BackgroundWe previously reported on increased bone strontium levels in dialysis patients with osteomalacia versus those presenting other types of renal osteodystrophy. A causal role of strontium in the development of osteomalacia was established in a chronic renal failure rat model.MethodsTo further elucidate the latter issue and to find out whether dialysis patients from particular centers/countries are at an increased risk for strontium accumulation, a worldwide multicenter study was established. In total, 834 patients from 34 dialysis centers in 23 countries were included. In each of the patients, a serum sample was taken for strontium determination, and water and dialysate samples were taken at the various steps of the water purification process. For each patient clinical data and for each center dialysis modalities were recorded.ResultsStrontium levels in serum of dialysis patients showed major differences between the various centers, ranging from mean values of 25 ± 8 μg/liter in the center with the lowest level up to 466 ± 90 μg/liter in the center with the highest concentration. It is of interest that these high levels were mainly found in developing countries. Furthermore, our data point toward a role of the final dialysate in the accumulation of the element, as indicated by the strong correlation (r = 0.74, P < 0.001) between mean serum and dialysate strontium levels. As the high tap water concentration of strontium was adequately reduced during the water purification process, contamination of the final dialysis fluid occurred by the addition of concentrates contaminated with strontium. Besides the dialysate, other factors, such as duration of dialysis, vitamin D supplements, or types of phosphate binders, played a less important role in the accumulation of the element.ConclusionsData of this multicenter study indicate patients of particular dialysis centers to be at an increased risk for strontium accumulation, the clinical consequence of which is under current investigation

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments.

Immunotargeting of PLAP-expressing tumours was studied for two radioiodinated, highly specific anti-PLAP monoclonal antibodies, 7E8 and 17E3, differing 10-fold in affinity, as well as for 7E8 F(ab')2 fragments. An anti-CEA monoclonal antibody or anti-CD3 F(ab')2 fragments were used as controls. Specific and non-specific targeting was examined in nude mice simultaneously grafted with PLAP-positive tumours derived from MO4 1-4 cells, and CEA-positive tumours, derived from 5583-S cells. Results indicated that (1) MO4 1-4 tumours, with a stable expression of PLAP on the plasma membrane, represent a useful new in vivo model for immunodirected tumour targeting; (2) differences in antibody affinity for PLAP in vitro are not reflected in antibody avidity for tumour cells in vivo; and (3) excellent selective and specific localisation of the PLAP-positive tumours is achieved when 7E8 F(ab')2 fragments are used. The high tumour/blood ratios (10.7 +/- 3.9 at 46 h after injection) were due to a much faster blood clearance of 7E8 F(ab')2 fragments. At this time point, the mean tumour/non-tumour tissue ratio was as high as 34.5, and the mean specific localisation index was 29.0. As expected, the F(ab')2 fragments provided high tumour imaging efficiency on gamma camera recording. These data imply important potentials of the PLAP/anti-PLAP system for immunolocalisation and therapy in patients, but also emphasise that in vitro criteria alone are not reflected in in vivo tumour localisation capacities of antibodies

Increased bone strontium levels in hemodialysis patients with osteomalacia

Increased bone strontium levels in hemodialysis patients with osteomalacia.BackgroundIn this study, we report on the association between increased bone strontium levels and the presence of osteomalacia in end-stage renal failure patients treated by hemodialysis.MethodsWe performed a histologic examination and determined the strontium content and strontium/calcium ratios in bone biopsies of 100 hemodialysis patients recruited from various centers all over the world. Aside from the bone strontium concentration, the bone aluminum content was assessed. The bone zinc concentration, a nonrelevant element for bone toxicity, was also measured.ResultsBone strontium levels and bone strontium/calcium ratios were increased in subjects with osteomalacia when compared with those with the other types of renal osteodystrophy. Bone strontium and bone calcium levels correlated with each other. The slope of the linear regression curve correlating these parameters was much steeper in the osteomalacic group (Y = 2.22X - 120) as compared with the other types of renal osteodystrophy (Y = 0.52X - 5.7). Within the group of patients with osteomalacia, bone strontium levels also significantly correlated with the bone aluminum content (r = 0.72, P = 0.018). No such correlation was found for the other types of renal osteodystrophy. The bone zinc concentration of subjects with normal renal function did not differ significantly from the values noted for the various types of renal osteodystrophy taken as separate groups, nor could increased bone zinc concentrations be associated with a particular bone lesion.ConclusionsOur data demonstrate an association between osteomalacia and increased bone strontium concentrations in dialysis patients. Further studies are warranted to establish whether strontium plays either a primary, secondary, or contributive role in the development of the latter type of renal osteodystrophy

Older Aboriginal Australians' Health Concerns and Preferences for Healthy Ageing Programs.

While there is strong evidence of the need for healthy ageing programs for older Aboriginal Australians, few are available. It is important to understand older Aboriginal Australians' perspectives on healthy ageing in order to co-design culturally-appropriate programs, including views on technology use in this context. Semi-structured interviews were conducted with 34 Aboriginal Australians aged 50 years and older from regional and urban communities to explore participants' health concerns, preferences for healthy ageing programs, and receptiveness to technology. Qualitative data were analyzed using a grounded theory approach. This study found that older Aboriginal Australians are concerned about chronic health conditions, social and emotional well-being, and difficulties accessing health services. A range of barriers and enablers to participation in current health programs were identified. From the perspective of older Aboriginal people, a successful healthy ageing program model includes physical and cognitive activities, social interaction, and health education. The program model also provides culturally safe care and transport for access as well as family, community, cultural identity, and empowerment regarding ageing well as central tenets. Technology could also be a viable approach for program delivery. These findings can be applied in the implementation and evaluation of culturally-appropriate, healthy ageing programs with older Aboriginal people

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

Concordance and Discordance Between Brain Perfusion and Atrophy in Frontotemporal Dementia

The aim of this study was to determine if a dissociation between reduced cerebral perfusion and gray matter (GM) atrophy exists in frontotemporal dementia (FTD). The study included 28 patients with FTD and 29 cognitive normal (CN) subjects. All subjects had MRI at 1.5 T, including T1-weighted structural and arterial spin labeling (ASL) perfusion imaging. Non-parametric concordance/discordance tests revealed that GM atrophy without hypoperfusion occurs in the premotor cortex in FTD whereas concordant GM atrophy and hypoperfusion changes are found in the right prefrontal cortex and bilateral medial frontal lobe. The results suggest that damage of brain function in FTD, assessed by ASL perfusion, can vary regionally despite widespread atrophy. Detection of discordance between brain perfusion and structure in FTD might aid diagnosis and staging of the disease

Complexity of global semianalytic sets in a real analytic manifold of dimension 2

Let X subset of R-n be a real analytic manifold of dimension 2. We study the stability index of X, s(X), that is the smallest integer s such that any basic open subset of X can be written using s global analytic functions. We show that s(X) = 2 as it happens in the semialgebraic case. Also, we prove that the Hormander-Lojasiewicz inequality and the Finiteness Theorem hold true in this context. Finally, we compute the stability index for basic closed subsets, S, and the invariants t and (t) over bar for the number of unions of open (resp. closed) basic sets required to describe any open (resp. closed) global semianalytic set

Is aristolochic acid nephropathy a widespread problem in developing countries? A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical - phytochemical approach

Ethnopharmacological relevance: Species of Aristolochia are associated with aristolochic acid nephropathy (AAN), a renal interstitial fibrosis and upper urinary tract cancer (UUC). Aristolochic acid nephropathy has been reported in ten countries but its true incidence is unknown and most likely underestimated. By combining an ethnobotanical and phytochemical approach we provide evidence for the risk of AAN occurring in Bangladesh. More specifically, we assess the intra-specific variation of aristolochic acid analogues in medicinally used A. indica samples from Bangladesh. Materials and Methods: Ethnobotanical information was collected from 16 kavirajes (traditional healers) in different study locations in Bangladesh. Plant samples were obtained from native habitats, botanical gardens, herbal markets and pharmaceutical companies. The samples were extracted using 70% methanol and were analysed using LC-DAD-MS and 1H-NMR. Results: Roots as well as leaves are commonly used for symptoms such as snake bites and sexual problems. Among the informants knowledge about toxicity or side effects is very limited and A. indica is often administered in very high doses. Replacement of A. indica with other medicinal plants such as Rauvolfia serpentina (L.) Benth. ex Kurz was common. A. indica samples contained a variety of aristolochic acid analogues such as aristolochic acid I, aristolochic acid II, cepharadione A and related compounds. Conclusions: AAN cases are likely to occur in Bangladesh and more awareness needs to be raised about the health risks associated with the use of A. indica and other species of Aristolochia as herbal medicines