Maternity services in the UK during the coronavirus disease 2019 pandemic: a national survey of modifications to standard care.

OBJECTIVE: To explore the modifications to maternity services across the UK, in response to the coronavirus disease 2019 (COVID-19) pandemic, in the context of the pandemic guidance issued by the Royal College of Obstetricians and Gynaecologists (RCOG), Royal College of Midwives (RCM) and NHS England. DESIGN: National survey. SETTING: UK maternity services during the COVID-19 pandemic. POPULATION OR SAMPLE: Healthcare professionals working within maternity services. METHODS: A national electronic survey was developed to investigate local modifications to general and specialist maternity care during the COVID-19 pandemic, in the context of the contemporaneous national pandemic guidance. After a pilot phase, the survey was distributed through professional networks by the RCOG and co-authors. The survey results were presented descriptively in tabular and graphic formats, with proportions compared using chi-square tests. MAIN OUTCOME MEASURES: Service modifications made during the pandemic. RESULTS: A total of 81 respondent sites, 42% of the 194 obstetric units in the UK, were included. They reported substantial and heterogeneous maternity service modifications. Seventy percent of units reported a reduction in antenatal appointments and 56% reported a reduction in postnatal appointments; 89% reported using remote consultation methods. A change to screening pathways for gestational diabetes mellitus was reported by 70%, and 59% had temporarily removed the offer of births at home or in a midwife-led unit. A reduction in emergency antenatal presentations was experienced by 86% of units. CONCLUSIONS: This national survey documents the extensive impact of the COVID-19 pandemic on maternity services in the UK. More research is needed to understand the impact on maternity outcomes and experience. TWEETABLE ABSTRACT: A national survey showed that UK maternity services were modified extensively and heterogeneously in response to COVID-19.

Modeling Water and Nutrient Movement in Sandy Soils Using HYDRUS-2D.

Models help to describe and predict complex processes and scenarios that are difficult to understand or measure in environmental management systems. Thus, model simulations were performed (i) to calibrate HYDRUS-2D for water and solute movement as a possible decision support system for Candler and Immokalee fine sand using data from microsprinkler and drip irrigation methods, (ii) to validate the performance of HYDRUS-2D using field data of microsprinkler and drip irrigation methods, and (iii) to investigate Br, NO, and water movement using annual or seasonal weather data and variable fertigation scenarios. The model showed reasonably good agreement between measured and simulated values for soil water content ( = 0.87-1.00), Br ( = 0.63-0.96), NO-N ( = 0.66-0.98), P ( = 0.25-0.78), and K ( = 0.44-0.99) movement. The model could be successfully used for scheduling irrigation and predicting nutrient leaching for both microsprinkler and drip irrigation systems on Florida's sandy soils.

An unusual cause of spinal bone loss detected by DXA scanning.

Routine DXA scanning in a 68-year-old asymptomatic man undergoing long-term bisphosphonate treatment for osteogenesis imperfecta showed unexplained loss of bone mineral density in two lumbar vertebrae. Subsequent radiographs revealed a 14-cm abdominal aortic aneurysm eroding the vertebrae. The importance of reviewing all the vertebrae in DXA scans is emphasized, and reasons for the absence of symptoms suggested.

Grapefruit Root and Rhizosphere Responses to Varying Planting Densities, Fertilizer Concentrations and Application Methods.

Huanglongbing (HLB) disease has caused a severe decline in citrus production globally over the past decade. There is a need for improved nutrient regimens to better manage the productivity of HLB-affected trees, as current guidelines are based on healthy trees. The aim of this study was to evaluate the effects of different fertilizer application methods and rates with different planting densities on HLB-affected citrus root and soil health. Plant material consisted of 'Ray Ruby' (Citrus × paradisi) grapefruit trees grafted on 'Kuharske' citrange (Citrus × sinensis × Citrus trifoliata). The study consisted of 4 foliar fertilizer treatments, which included 0×, 1.5×, 3× and 6× the University of Florida Institute of Food and Agriculture (UF/IFAS) recommended guidelines for B, Mn and Zn. Additionally, 2 ground-applied fertilizer treatments were used, specifically controlled-release fertilizer (CRF1): 12-3-14 + B, Fe, Mn and Zn micronutrients at 1× UF/IFAS recommendation, and (CRF2): 12-3-14 + 2× Mg + 3× B, Fe, Mn and Zn micronutrients, with micronutrients applied as sulfur-coated products. The planting densities implemented were low (300 trees ha-1), medium (440 trees ha-1) and high (975 trees ha-1). The CRF fertilizer resulted in greater soil nutrient concentrations through all of the time sampling points, with significant differences in soil Zn and Mn. Grapefruit treated with ground-applied CRF2 and 3× foliar fertilizers resulted in the greatest bacterial alpha and beta diversity in the rhizosphere. Significantly greater abundances of Rhizobiales and Vicinamibacterales were found in the grapefruit rhizosphere of trees treated with 0× UF/IFAS foliar fertilizer compared to higher doses of foliar fertilizers.

Health-related quality of life in patients with osteoporosis in the absence of vertebral fracture: a systematic review.

To review whether osteoporosis in the absence of vertebral fracture (VFX) affects health-related quality of life (HRQoL), a systematic search of the main literature databases for HRQoL in patients with osteoporosis without VFX was undertaken. This was undertaken. This identified 1,327 articles as potentially relevant to the review. After screening of abstracts and reviewing 168 articles in detail, 27 were considered relevant. HRQoL data were extracted and collated into tables and, where possible, were converted into normative scores and further analysed. Data relating to the associations between HRQoL and bone mineral density (BMD) were also collated. Of the 27 articles included, only 5 directly compared osteoporosis without VFX with a control group (BMD T-score > -1.0, without VFX). Extracted raw data from 21 articles demonstrated that patients with osteoporosis without VFX had clinically relevant reductions in role physical, general health, vitality, mental health domains and the mental component summary score, using SF36. Using Qualeffo-41, pain and physical function were worse in these patients. Also, HRQoL was related to upper femur, but not lumbar spine BMD. HRQoL data in patients with osteoporosis without VFX are limited and variable but suggest that HRQoL is adversely affected by osteoporosis in the absence of VFX. The association of lower BMD and worse HRQoL suggests that more attention should be paid to HRQoL in those without VFX. Future studies are needed to investigate HRQoL in patients with osteoporosis in the absence of fracture, controlling for co-morbidities and social and economic status.

Micronutrients Improve Growth and Development of HLB-Affected Citrus Trees in Florida.

Enhanced nutritional programs (ENPs) have improved citrus trees' growth and development in the era of Huanglongbing (HLB). Studies conducted with variable rates of manganese (Mn) and Iron (Fe) on young HLB-affected citrus trees showed that applying double the standard recommendation increased growth and biomass accumulation. Since HLB is believed to cause deficiency symptoms of micronutrients in citrus trees, it is critical to ensure their optimal levels in the leaves. This could be achieved by soil application of either a Mn rate of 8.9 to 11.5 kg ha-1 as MnSO4 (31%) for young HLB-affected 'Valencia' (Citrus sinensis (L.) Osbeck) citrus trees or an Fe rate of 9.6 to 11.8 kg ha-1 as Ferrous sulfate heptahydrate (20%) for 'Bingo' (Citrus reticulata, Blanco) citrus trees. Maintaining optimal levels of these micronutrients may enable citrus trees to carry out photosynthetic activities to ensure growth and development. It may also help the tree in the regulation of various physiological processes as part of the antioxidant enzyme Mn-superoxidase dismutase (SOD). Micronutrient manipulation through variable rates of fertilizer application to influence nutrient availability is an important mitigating factor for HLB-affected citrus trees and an integral component of citrus production in Florida.

Boron, Manganese, and Zinc Sorption and Leaf Uptake on Citrus Cultivated on a Sandy Soil.

Solute fate in soil-plant continuum could either be soil or leaf uptake or leaching beyond the rooting zone. An adsorption coefficient (KD) is an important chemical property to describe the interaction between the solute and soil, affecting the solute movement in soils from one point to another. Boron (B), manganese (Mn), and zinc (Zn) uptake are evident in the leaves as a constituent of photosynthesis and other plant body-building mechanisms for growth and development. This study investigates the availability of micronutrients (B, Mn, and Zn) to citrus trees through modified application methods and rates. Leaf samples were collected from experimental plots arranged in a randomized complete block design, with 4 micronutrient treatments: control, foliar ×1, foliar ×2, and soil ×1. Boron, Mn, and Zn rates were 1.12, 10.08, and 5.60 kg ha-1, respectively. Composite soil samples were randomly collected at 5 points, and a 1-point adsorption study was conducted in 4 soil depths at an increment of 15 cm from the soil surface. Adsorption coefficient (KD) for Mn and B was 22 and 3 times higher at 0-15 cm than at soil depth of 15-60 cm. The adsorption coefficient (KD) for Zn was 2.5 times greater at 0-15 cm than 15-30 cm soil depth, while there was little or no sorption at 30-60 cm. Leaf Mn and Zn concentrations showed that foliar spray was 2 times higher than the soil application method, while B showed that the soil application method was 2 times higher than foliar application method for 2 seasons sampling events. Thus, the behavior of B, Mn, and Zn in the soil via adsorption coefficient (KD) reflects the availability of B, Mn, and Zn in the citrus leaves.

Root-Shoot Nutrient Dynamics of Huanglongbing-Affected Grapefruit Trees.

With huanglongbing (HLB) causing a reduction in fine root mass early in disease progression, HLB-affected trees have lower nutrient uptake capability. Questions regarding the uptake efficiency of certain fertilizer application methods have been raised. Therefore, the goals of this study are to determine if nutrient management methods impact nutrient translocation and identify where in the tree nutrients are translocated. Destructive nutrient and biomass analysis were conducted on field grown HLB-affected grapefruit trees (Citrus × paradisi) grafted on 'sour orange' (Citrus × aurantium) rootstock under different fertilizer application methods. Fertilizer was applied in the form of either 100% soluble granular fertilizer, controlled release fertilizer (CRF), or liquid fertilizer. After three years, the entire tree was removed from the grove, dissected into eight different components (feeder roots, lateral roots, structural roots, trunk, primary branches, secondary branches, twigs, and leaves), weighed, and then analyzed for nutrient contents. Overall, application methods showed differences in nutrient allocation in leaf, twig, and feeder root; however, no consistent pattern was observed. Additionally, leaf, twig, and feeder roots had higher amount of nutrients compared to the other tree components. This study showed that fertilization methods do impact nutrient contents in different components of HLB-affected trees. Further research should be conducted on the impact of different fertilizer application methods and rates on HLB-affected trees.

Integrated Water, Nutrient, and Pesticide Management of Huanglongbing-Affected Sweet Oranges on Florida Sandy Soils-A Review.

Citrus greening (huanglonbing (HLB)) disease has drastically reduced citrus fruit production in Florida over the last two decades. Scientists have developed sustainable nutrient management practices to live with the disease and continue fruit production. Best pesticide management practices have been devised to reduce the spread of HLB by Asian citrus psyllid (ACP). However, soil application of excessive nutrients and the use of soil drench application of pesticides to huanglongbing-infected citrus groves have been a serious environmental concern since the recent development of resistance to some pesticides. It is important to understand the consequences of applying pesticides and nutrients beyond the recommended application rates with an inappropriate method for citrus growth and development. Alternatively, foliar sprays of some nutrients proved effective to meet plants' requirements, and foliar sprays of effective insecticide products could provide an adequate mode of action for group rotation to minimize insecticide resistance by ACP and other pests. Sustainability in citrus production systems should include best management practices that improve pesticide and nutrient efficiency by including the total maximum daily load exiting the grove to reduce pesticide and nutrient exports into waterbodies.

The Effect of Foliar and Ground-Applied Essential Nutrients on Huanglongbing-Affected Mature Citrus Trees.

The fate of foliar and ground-applied essential nutrients is the least studied topic under citrus greening or Huanglongbing (HLB)-affected citrus, which is inherently suffering from severe root decline because of HLB-associated problems. The objective of this study was to evaluate if ground-applied coupled with foliar spray of essential nutrients can reverse the decline in tree growth and understand the fate of the nutrients in the soil-root-tree interfaces. The treatments were arranged in a split-split plot design in which nitrogen (N) was ground-applied in 20 splits biweekly and Mn, Zn, and B were foliar and /or ground-applied in three splits following the spring, summer, and late summer flush seasons. Soil nutrients in three depths (0-15, 15-30, and 30-45 cm), root, and leaf nutrient concentrations of the essential nutrients, leaf area index (LAI), and tree canopy volume (TCV) data were studied twice (spring and summer) for two years. A significantly higher soil NH4-N and NO3-N concentrations were detected in the topsoil depth than the two lower soil depths (15-30 and 30-45 cm) indicating lesser nutrient leaching as trees received moderate (224 kg ha-1) N rate. Except for soil zinc (Zn) concentration, all the nutrient concentrations were significantly higher in the topsoil (0-15 cm), compared with two lower soil depths indicating that Zn was intricate by changes in soil environmental conditions, root acquisition, and/or leaching to lower soil depth. Leaf N concentration significantly increased over time following seasonal environmental fluctuations, tree growth, and development. Thus, leaf N concentration remained above the optimum nutrient range implying lower N requirement under irrigation scheduling with SmartIrrigation, an App used to determine the daily irrigation duration to meet tree water requirement and split fertigation techniques. Root Manganese (Mn) and Zn concentrations were significantly higher in the root tissues of the treated than the control trees and translocated to the leaves accordingly. Meanwhile, a significantly higher LAI for trees budded on Swingle (Swc) rootstock however, larger TCV for trees budded on Volkameriana (Volk) rootstocks. The trees had significantly larger TCV when the trees received a moderate N rate during early study years and under foliar 9 kg ha-1 coupled with the ground 9 kg ha-1 Mn and Zn treatments during the late study years. Therefore, split ground application of 224 kg ha-1 of N, foliar applied 9 kg ha-1 coupled with ground-applied 9 kg ha-1 Mn and Zn were the suggested rates to sustain the essential leaf nutrient concentration within the optimum ranges and improve the deterioration of vegetative growth associated with HLB-induced problems of citrus trees.

Double-headed small-bowel capsule endoscopy: Real-world experience from a multi-centre British study.

INTRODUCTION: Capsule endoscopy (CE) is well established the investigation of small-bowel (SB) pathology. We compared the use of double-headed (DH) capsules, to conventional single-headed (SH), in a real-world patient cohort in the first multicentre British study. METHODS: Over 9 months, patients referred for routine SBCE at 4 tertiary referral centres in the UK underwent DH CE instead of conventional SH using MiroCamⓇ MC2000 as per local protocols. One head (L/R) was chosen at random and reported by an expert reviewer. The DH recordings, anonymised and randomised, reported by another expert or re-read after a 4-week interval. For each CE, numbers and types of findings and overall conclusion/diagnosis were compared between SH and DH examinations. RESULTS: 211 CEs were performed. 7 failed to reach the SB; 204 analysed. Indications were: SB bleeding (n = 94); ?SB inflammation or reassessment of known inflammatory bowel disease (IBD) (n = 84); ?SB neoplasia including suspicious radiological imaging (n = 15); and, others e.g. ?celiac disease (n = 11). For SB bleeding: 27/94 (28.7%) examinations reported differences between SH and DH readings. In 17 (18.1%) the findings were clinically significant. SH CE missed angiectasias (5 pts), SB inflammation (7 pts), oesophagitis (2 pts) and SB masses (2 pts). In 1 patient, the extent of angiectasias seen was greater on the DH reading. For IBD: findings differed in 30/84 (35.7%) of CEs; 11 (13.1%) were clinically significant. In 5, signs of active inflammation were missed by the SH reading. In 6, assessment of extent/severity differed. For?SB neoplasia findings differed in 2/15 (13.3%) of examinations. Both were clinically significant. For others: 1/11 (9.1%) examinations differed; however, not deemed clinically significant. Overall, use of DH CE impacted the diagnosis in 30/204 (14.7%). CONCLUSIONS: The use of DH CE provides more information with the potential to change clinical diagnosis and therefore management. Therefore, the routine adoption of DH CE in SB assessment should be considered.

Leaching losses from blueberries grown in sandy soils amended with pine bark.

Leaching of irrigation water from blueberry (Vaccinium spp.) plants intensifies when sandy soils are amended with pine (Pinus spp.) bark. In a greenhouse study, leaching fractions of water (LFW) and nutrients (LFN) were determined from two blueberry (V. corymbosum L.) cultivars, 'Emerald' and 'Jewel', grown in biochar-treated and nontreated sandy subsoil and irrigated with drip emitters using one of three pulse frequencies in a factorial design. The LFW was >50% under Emerald and <20% under Jewel, which has a more extensive root system. When the frequency of same volume of irrigation was increased from 2 (F2) to 10 (F10) pulses per day, the average LFW decreased from 46 to 30%. The LFN from a single fertigation was much lower than the total LFN after 6 d of irrigations applied between two fertigation events. The LFN increased linearly with LFW. Amending subsoil with 2% biochar increased soil pH, limited root growth, and did not reduce nutrient leaching. Eighteen months after plant establishment, 1.9% of applied NO3 --N and 2.5% of applied PO4 3--P from Emerald and 0.8 and 1.0%, respectively, from Jewel leached below the root zone during a fertigation event. During irrigations following a fertigation event, 10.5% of both NO3 --N and PO4 3--P from Emerald and 3.0 and 2.5% from Jewel leached below the root zone. All growth parameters including root/shoot ratio were higher in Jewel than Emerald. This study indicated that leaching rates could be reduced by selecting blueberry cultivars with a dense root system and using a drip irrigation system with >5 pulses d-1 to supply the daily water requirements in pine bark-amended sandy soil.

Effect of Essential Nutrients on Roots Growth and Lifespan of Huanglongbing Affected Citrus Trees.

Understanding citrus tree root development and dynamics are critical in determining crop best nutrient management practices. The role of calcium (Ca) and magnesium (Mg), manganese (Mn), Zinc (Zn), and boron (B) on huanglongbing (HLB) affected citrus trees' root growth and lifespan in Florida is not fully documented. Thus, the objective of this study was to determine the impact of foliar and ground-applied essential nutrients on seasonal fine root length density (FRLD; diameter (d) < 2 mm) and coarse roots (d > 2 mm), FRLD dynamics, root survival probability (lifespan), and root-zone soil pH of HLB-affected sweet orange trees. Results indicated that Ca treated trees budded on Cleopatra (Cleo) and Ca and Mg combined treatments on Swingle (Swc) rootstocks significantly increased seasonal FRLD of fine (< 2 mm) and coarse roots. The highest median root lifespan of Ca treated trees was 325 and 339 days for trees budded on Cleo and Swc rootstocks, respectively. In the second study, the coarse roots showed a significantly higher reaction to the nutrition applied than the fine roots. Meanwhile, the 2× (1× foliar and 1× ground-applied) treated trees showed a significantly higher median root lifespan compared to the other treatments. Thus, the current study unwraps future studies highlighting the combined soil and/or foliar application of the above nutrients to stimulate FRLD and improve root lifespan on HLB-affected sweet oranges with emphasis on root-zone soil pH.

Imidacloprid transport and sorption nonequilibrium in single and multilayered columns of Immokalee fine sand.

Imidacloprid (IMD) is a neonicotinoid pesticide soil-drenched to many crops to control piercing-sucking insects such as the Asian citrus psyllid (ACP). Neonicotinoids are persistent in the environment and transport analyses are helpful estimate leaching potential from soils that could result in groundwater pollution. The objective of this study was to analyze IMD breakthrough under saturated water flow in soil columns packed with three horizons (A, E, Bh) of Immokalee Fine Sand (IFS). Also, we used the dimensionless form of the convective-dispersive model (CD-Model) to compare the optimized transport parameters from each column experiment (retardation factor, R; fraction of instantaneous-to-total retardation, ß; and mass transfer coefficient, ω) with the parameters obtained from sorption batch equilibria and sorption kinetics. The tracer (Cl-) breakthrough curves (BTCs) were symmetrical and properly described by the CD-Model. IMD BTCs from A, Bh, and multilayered [A+E+Bh] soil columns showed steep fronts and tailing that were well described by the one-site nonequilibrium (OSNE) model, which was an evidence of non-ideal transport due to IMD mass transfer into the soil organic matter. In general, IMD was weakly-sorbed in the A and Bh horizons (R values of 3.72 ± 0.04 and 3.08 ± 0.07, respectively), and almost no retardation was observed in the E horizon (R = 1.20 ± 0.02) due to its low organic matter content (0.3%). Using the HYDRUS-1D package, optimized parameters (R, ß, ω) from the individual columns successfully simulated IMD transport in a multilayered column mimicking an IFS soil profile. These column studies and corresponding simulations agreed with previous findings from batch sorption equilibria and kinetics experiments, where IMD showed one-site kinetic mass transfer between soil surfaces and soil solution. Ideally, sandy soils should be maintained unsaturated by crop irrigation systems and rainfall monitoring during and after soil-drench application. The unsaturated soil will increase IMD retardation factors and residence time for plant uptake, lowering leaching potential from soil layers with low sorption capacity, such as the E horizon.

Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells.

Glucocorticoids are effective anti-inflammatory and immunosuppressive agents, but their use is often associated with debilitating side effects such as glucocorticoid-induced osteoporosis. Newly developed glucocorticoid analogues such as the so-called dissociated glucocorticoids are potent immunosuppressants and have the potential for fewer side effects. The effects of these new analogues on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in osteoblastic cells have not been studied. OPG and RANKL are osteoblast-derived proteins pivotal to the regulation of bone mass. RANKL stimulates bone resorption by increasing osteoclast differentiation, activation and survival. OPG is the decoy receptor for RANKL and thus inhibits bone resorption. Here, we show that dexamethasone, prednisolone, deflazacort and the dissociated glucocorticoids, RU24858, RU40066, RU24782, AL438-F1 and ZK216348 significantly inhibit OPG production in two human osteoblastic cell lines (MG63 and hFOB). The potency for OPG inhibition was ligand and cell-type specific. In both cell types, dexamethasone and prednisolone were the most potent ligands inhibiting OPG production with IC(50)s of approximately 0.1 nM and 10 nM respectively. In MG63 cells, deflazacort and the RU compounds were the next most potent ligands followed by AL438-F1 and ZK216348. In hFOB cells, however, the RU compounds were the least potent ligands with an IC(50) 74 times higher than in MG63 cells. In contrast, the level of maximum inhibition or effectiveness of OPG inhibition did not vary between cell types but did vary according to the ligand. Dexamethasone, prednisolone, deflazacort and the RU compounds all inhibited OPG production by a maximum of approximately 70-80%, whereas AL438-F1 and ZK 216348 inhibited OPG production by a maximum of only 40-50% at 1 microM. All of the dissociated glucocorticoids and deflazacort were poor stimulators of RANKL gene expression stimulating by only approximately 1-3-fold compared to 7-fold by prednisolone. These data demonstrate that deflazacort and the dissociated glucocorticoids are weak stimulators of the RANKL:OPG ratio compared to prednisolone. Therefore, these compounds have the potential to cause less bone loss than that seen with prednisolone, though this was not investigated here.

A bio-assay for effectors of osteoclast differentiation in serum from patients with bone disease.

UNLABELLED: Osteoclast differentiation and activity, and hence bone loss, depend on two opposing cytokines. Receptor activator of NF-(kappa)B ligand (RANKL) produced by osteoblasts and T-cells stimulates, while osteoprotegerin inhibits. Both of these cytokines are found in serum. Our aim was to develop a functional assay for any factors present in human serum that can affect osteoclast differentiation and to assess whether any such factors vary in diseases in which bone loss occurs. METHODS: Using a culture model of osteoclast differentiation in the presence of macrophage colony stimulating factor and soluble RANKL, we have measured the effects of different human sera on osteoclast differentiation. The production of a marker enzyme for the osteoclast, tartrate-resistant acid phosphatase (TRAP), was used to follow osteoclast differentiation. RESULTS: In general, human serum stimulates osteoclast differentiation as indicated by TRAP activity, but in patients with low bone density this stimulation was attenuated. Sera from 40 female subjects with low bone mineral density showed significantly lower TRAP cell differentiation activity than sera from the healthy female controls. CONCLUSION: We describe a functional bio-assay for factors in human serum which can affect osteoclast differentiation. This assay may have application in monitoring the effects of therapy in bone disease.

Effects of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate on mouse osteoclasts.

A group of 5-day-old mice were injected intraperitoneally with (3-amino-1-hydroxypropylidine)-1,1-bisphosphonate (APD). Morphologic changes were observed in vitally stained osteoclasts on parietal bones 3 days later, and these were judged to be degenerative. At this time significantly increased numbers of nuclei per osteoclast and total numbers of osteoclast nuclei were observed. However, at 4 days after the injection of APD, the total numbers of osteoclasts were significantly reduced relative to controls. When parietal bones were maintained in culture, APD reduced osteoclast numbers and inhibited cell-mediated 45Ca2+ release. Exposure of bones to parathyroid hormone increased the number of osteoclasts counted 1 day later. This effect was not blocked by APD. Calcitonin prevented the reduction in osteoclast numbers due to APD in vitro. We conclude that APD has a direct effect on resorbing mouse osteoclasts.

Isoforms of bone alkaline phosphatase: characterization and origin in human trabecular and cortical bone.

Alkaline phosphatase (ALP) is a glycoprotein and functions as an ectoenzyme attached to the cell membrane by a hydrophobic glycosyl-phosphatidylinositol (GPI) anchor. Three bone ALP (BALP) isoforms in human serum were separated and quantitated by high-performance liquid chromatography. B/I, a minor fraction, is composed on average of bone (70%) and intestinal (30%) ALP, and two major isoforms, B1 and B2. Treatment with GPI-specific phospholipase C (GPI-PLC) did not influence the activities or retention times for B1 and B2, indicating that the biochemical differences between B1 and B2 are likely to be due to different glycosylation patterns. The B/I fraction in serum, on average 4% of total ALP, was found to be composed of B1 and B2 isoforms, each with an intact hydrophobic GPI cell membrane anchor. We investigated the origin of these three BALP isoforms and osteocalcin in human femora from five healthy individuals (four males), mean age 51 years, obtained from a tissue bank. Bone was sampled from three sites: cortical bone, trabecular bone from the diaphysis, and trabecular bone from the greater trochanter. Trabecular bone, from both sites, had higher BALP activities compared with cortical bone. Conversely, the osteocalcin content of cortical bone was more than 3-fold greater than that of trabecular bone. Cortical bone had approximately 2-fold higher activity of B1 compared with B2, whereas trabecular bone had approximately 2-fold higher activity of B2 compared with B1. We observed a previously undescribed BALP isoform (B1x) in all bone samples. B1x was also observed in sera from some patients (60%) with severe renal insufficiency and on chronic dialysis therapy (n = 20). The isoforms of BALP may provide information relating to bone metabolism within specific bone compartments.