Phosphorus Imbalance Research Articles

Biological effects of MRI contrast agents: gadolinium retention, potential mechanisms and a role for phosphorus.

No discussion of challenges for chemistry in molecular imaging would be complete without addressing the elephant in the room-which is that the purest of chemical compounds needs to interact with a biological system in a manner that does not perturb normal biology while still providing efficacious feedback to assist in diagnosis of disease. In the past decade, magnetic resonance imaging (MRI) agents long considered inert have produced adverse effects in certain patient populations under certain treatment regimens. More recently, inert blood pool agents have been found to deposit in the brain. Release of free metal is often suspected as the culprit but that hypothesis has yet to be validated. In addition, even innocuous agents can cause painful side effects during injection in some patients. In this brief review, we summarize known biological effects for gadolinium- and iron-based MRI contrast agents, and discuss some of the potential mechanisms for the observed biological effects, including the potential role of phosphorus imbalance, related to kidney disease or cancer, in destabilizing gadolinium-based chelates and precipitating free gadolinium.This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

Soft Tissue Mineralization in Captive 2-Toed Sloths.

Soft tissue mineralization was diagnosed in 19 captive 2-toed sloths (Choloepus didactylusandCholoepus hoffmanni) ranging from 2 months to 41 years of age. Gross mineralization was evident at necropsy in 6 of 19 sloths and was prominent in the aorta and arteries. Histologically, 11 sloths had arterial mineralization, including mural osseous and chondroid metaplasia and smooth muscle hyperplasia consistent with arteriosclerosis. Visceral mineralization most commonly involved the gastric mucosa (17 sloths), kidneys (17 sloths), and lungs (8 sloths). Eleven sloths ranging in age from 5 to 41 years old had moderate to severe renal disease, which may be an important underlying cause of soft tissue mineralization in adult sloths. However, 5 sloths (juveniles and adults) had severe soft tissue mineralization with histologically normal kidneys or only mild interstitial inflammation or fibrosis, suggesting other causes of calcium and phosphorus imbalance. Degenerative cardiac disease was a common finding in 10 sloths with vascular mineralization and varied from mild to severe with fibrosis and acute noninflammatory myocardial necrosis. Although the prevalence of cardiac disease in adult sloths has not been documented, disease may be exacerbated by hypertension from degenerative arteriosclerosis as noted in this study group. Although renal disease likely contributed substantially to mineralization of tissues in most sloths in this study, nutritional causes of soft tissue mineralization-such as imbalances in dietary vitamin D or calcium and phosphorus-may be an important contributing factor.

Comparing the expression patterns of placental magnesium/phosphorus-transporting channels between healthy and preeclamptic pregnancies.

Preeclampsia is a pregnancy-specific disorder characterized by de novo development of concurrent hypertension, proteinuria, and placental oxidative stress. During the last trimester of gestation, maternal-to-fetal transport of minerals is dramatically increased and becomes tightly mediated by ion channels that are highly permeable to various divalent cations, such as Ca(2+) , Mg(2+) , and Zn(2+) . The regulation of magnesium/inorganic phosphorus ion-channel transport in the placenta, however, is not incompletely understood. In the present study, we examined the regulation of magnesium/inorganic phosphorus channels (MPCs) in the placenta of pregnant women suffering from preeclampsia as well as in primary human placental cells subjected to oxidative stress. The expression of MPC genes (TRPM6, TRPM7, PiT-1, and PiT-2) was down-regulated in preeclamptic placenta tissues during preterm labor, and generally remained lower at term labor-although TRPM7 expression in the central placenta or PiT-2 expression in whole placenta was unchanged or up-regulated. Consistent with this association, expression of MPC genes in the primary placental cells was reduced under hypoxic conditions. TRPM6, TRPM7, and PiT-1 channels were predominantly detected in the syncytiotrophoblast layers of the placenta. In contrast, PiT-2 was abundant in the placental intravillous connective tissues. Taken together, our findings indicated that placental MPC expression is down-regulated in cases of preeclampsia and under hypoxia. This relationship may contribute to a better understanding of the interrelationship between magnesium/inorganic phosphorus imbalances and preeclampsia development during preterm or term labor.

Responses of soil nutrient concentrations and stoichiometry to different human land uses in a subtropical tidal wetland

We studied the impacts of anthropogenic changes in land use on the stoichiometric imbalance of soil carbon (C), nitrogen (N), phosphorus (P) and potassium (K) in Phragmites australis wetlands in the Minjiang River estuary. We compared five areas with different land uses: P. australis wetland (control), grassland, a mudskipper breeding flat, pond aquaculture and rice cropland. Human activity has affected the elemental and stoichiometric compositions of soils through changes in land use. In general, soil C and N concentrations were lower and total soil K concentrations were higher at the sites under human land uses relative to the control site, and total soil P concentrations were generally not significantly different. The close relationship between total soil C and N concentrations in all cases, including fertilization with N, suggested that N was the most limiting nutrient in these wetlands. Lower soil N concentrations and similar soil P concentrations and higher soil K concentrations under human land-use activities suggest that human activity has increased the role of N limitation in these wetlands. Only grassland use increases soil N contents (only in the 0–10cm of soil). Despite N fertilization, lower soil N concentrations were also observed in the rice cropland, indicating the difficulty of avoiding N limitation in these wetlands. The observed lower soil N:P ratio, together with higher soil P and K availabilities in rice croplands, is consistent with the tendency of human activity to change the competitive relationships of plants, in this case favoring species adapted to high rates of growth (low N:P ratio) and/or favoring plants with high demands for P and K. Both, soil C storage and respiration were higher in grasslands, likely due to the introduction of grasses, which led to a high density of plants, increased grazing activity and soil compaction. Soil C storage and respiration were lower under human land uses, except in the rice cropland, with respect to natural wetland. Using overall data, soil C storage and respiration were correlated, indicating that soil respiration was correlated with plant productivity. In this wetland area the impacts of different human land-uses on soil stoichiometry and C-cycle can be very different depending on the activity. Further regeneration of natural communities can be determined by the previous type of land-use.

Biogeochemical indicators of elevated nitrogen deposition in semiarid Mediterranean ecosystems.

Nitrogen (N) deposition has doubled the natural N inputs received by ecosystems through biological N fixation and is currently a global problem that is affecting the Mediterranean regions. We evaluated the existing relationships between increased atmospheric N deposition and biogeochemical indicators related to soil chemical factors and cryptogam species across semiarid central, southern, and eastern Spain. The cryptogam species studied were the biocrust-forming species Pleurochaete squarrosa (moss) and Cladonia foliacea (lichen). Sampling sites were chosen in Quercus coccifera (kermes oak) shrublands and Pinus halepensis (Aleppo pine) forests to cover a range of inorganic N deposition representative of the levels found in the Iberian Peninsula (between 4.4 and 8.1 kg N ha(-1) year(-1)). We extended the ambient N deposition gradient by including experimental plots to which N had been added for 3 years at rates of 10, 20, and 50 kg N ha(-1) year(-1). Overall, N deposition (extant plus simulated) increased soil inorganic N availability and caused soil acidification. Nitrogen deposition increased phosphomonoesterase (PME) enzyme activity and PME/nitrate reductase (NR) ratio in both species, whereas the NR activity was reduced only in the moss. Responses of PME and NR activities were attributed to an induced N to phosphorus imbalance and to N saturation, respectively. When only considering the ambient N deposition, soil organic C and N contents were positively related to N deposition, a response driven by pine forests. The PME/NR ratios of the moss were better predictors of N deposition rates than PME or NR activities alone in shrublands, whereas no correlation between N deposition and the lichen physiology was observed. We conclude that integrative physiological measurements, such as PME/NR ratios, measured on sensitive species such as P. squarrosa, can provide useful data for national-scale biomonitoring programs, whereas soil acidification and soil C and N storage could be useful as additional corroborating ecosystem indicators of chronic N pollution.

Impacts of increased nitrogen deposition and altered precipitation regimes on soil fertility and functioning in semiarid Mediterranean shrublands

We studied the impacts of nitrogen (N) deposition and precipitation gradients on soil chemistry and functioning of calcareous soils from semiarid Mediterranean shrublands. Under greenhouse conditions, N fertilization at 0, 10, 20 and 50 kg N ha−1 yr−1 and low water increased inorganic N. The concentration of extractable cations was higher under low water due to reduced leaching, whereas soil carbon (C) to N ratio was affected by the interaction of N fertilization and water supply, suggesting the role of rainfall in the response of soil C and N storage capacity to N deposition. Soil phosphatase activity increased with N as a consequence of an induced N to phosphorus imbalance, whereas N-fixation was down-regulated by N fertilization, a response attributed to high levels of nitrate. Net N mineralization and nitrification were also reduced by N fertilization. Under field conditions, N availability was positively related to the N deposition gradient (3.98–6.05 kg N ha−1 yr−1). Nutrient availability was primarily and positively related to rainfall and temperature, although N deposition contributed to an overall cation depletion. Finally, we suggest the importance of conducting additional studies on the effects of N deposition and climate change on calcareous soils in Mediterranean ecosystems.

Human-induced nitrogen–phosphorus imbalances alter natural and managed ecosystems across the globe

The availability of carbon from rising atmospheric carbon dioxide levels and of nitrogen from various human-induced inputs to ecosystems is continuously increasing; however, these increases are not paralleled by a similar increase in phosphorus inputs. The inexorable change in the stoichiometry of carbon and nitrogen relative to phosphorus has no equivalent in Earth's history. Here we report the profound and yet uncertain consequences of the human imprint on the phosphorus cycle and nitrogen:phosphorus stoichiometry for the structure, functioning and diversity of terrestrial and aquatic organisms and ecosystems. A mass balance approach is used to show that limited phosphorus and nitrogen availability are likely to jointly reduce future carbon storage by natural ecosystems during this century. Further, if phosphorus fertilizers cannot be made increasingly accessible, the crop yields projections of the Millennium Ecosystem Assessment imply an increase of the nutrient deficit in developing regions.

Seasonal fluxes of phosphate across the sediment-water interface in Edku Lagoon, Egypt

Edku Lagoon is a shallow, brackish, coastal wetland located in the north-western part of the Nile Delta. It suffers from a high level of eutrophication, owing to the heavy load of nutrients, especially phosphorus. The purpose of this paper was to study the flux rates of organic and inorganic phosphorus across the sediment water interface in Edku Lagoon. Both the organic and inorganic phosphorus of surface sediments, pore water and their concentrations in the water just above the sediments were used to calculate the flux rates and to derive the geochemical models. These suggest that, at present, the flux of inorganic and organic phosphorus is from water to sediments via the sedimentation of inorganic particles and organic matter. The results show that phosphorus deposition to the sediments exceeds the rate of inorganic phosphorus release from the sediments to the water column. In a steady state, the rates of organic phosphorus release more or less match the rates of deposition. These reflect the imbalance (accumulation) of phosphorus in the geochemical cycle in the lagoon and its highly eutrophic status. Efforts to control the eutrophication of Edku Lagoon have focused on reducing the phosphorus input.

Złośliwa osteopetroza niemowlęca – opis przypadku

Malignant infantile osteopetrosis is a rare inherited via the autosomal recessive pattern metabolic disease caused by osteoclast failure leading to failed bone resorption. The symptoms appear within the first months of life and result from abnormal bone structure, obliteration of the marrow cavity and bone marrow failure, they include: anemia, thrombocytopenia, a tendency to recurrent infections, hepatosplenomegaly. There is also calcium and phosphorus imbalance, an increased bone fragility. Progressive bony encroachment of the cranial nerves leads to pressure on them, which clinically manifests as nystagmus, stranismus, blindness and deafness. Patients usually die of untreated infectious causes. The diagnosis is confirmed by X-ray skeletal survey, which showes generalized osteosclerosis. The only curative treatment of patients with osteopetrosis is an allogeneic bone marrow transplantation.In this article we describe diagnostic difficulties in the diagnosis of malignant infantile osteopetrosis in a 6-month-old girl.

The Influence of Dietary Calcium and Phosphorus Imbalance on Intestinal NaPi-IIb and Calbindin mRNA Expression and Tibia Parameters of Broilers.

A 2×2 factorial experiment was conducted to study the effect of dietary calcium and non-phytate phosphorus (nPP) imbalance on calbindin and NaPi-IIb mRNA levels in the small intestine and tibia parameters of broiler chicks. One hundred and forty four 1-d-old Arbor Acres male broiler chicks were divided into four treatments consisted of six replicates with six chicks each. The two dietary calcium levels were 1.10% and 0.60%, and two dietary nPP levels were 0.50% and 0.27%. Results showed that a high Ca/nPP ratio diet (4.07:1) significantly depressed feed intake and weight gain of broilers (p<0.05), but a lower Ca:nPP ratio (1.2:1) had no influence (p>0.05). Low-Ca with low-P diet resulted in low tibia minerals and tibia breaking strength of broilers, and all the tibia parameters were further decreased when the dietary ratio of Ca to P was relative higher. Low dietary Ca or P up-regulated the calbindin and NaPi-IIb mRNA expression levels. Low Ca with normal P diet up-regulated duodenal calbindin mRNA expression level to the greatest extent. Low P with a normal Ca diet significantly enhanced NaPi-IIb mRNA expression level to the highest extent. These results suggest that the calbindin and NaPi-IIb mRNA expression were enhanced by the imbalance between dietary Ca and nPP, and their expression were not only influenced by Ca or nPP level, but also the ratio of Ca:nPP.

Identifying and controlling critical sources of farm phosphorus imbalances for Vermont dairy farms

Lake Champlain, located between Vermont, New York, and Quebec exhibits eutrophication mainly due to continuing phosphorus (P) losses from upstream nonpoint source areas. Several state and local agencies have initiated efforts aimed at assessing and identifying critical sources areas for P loss. To augment these efforts, accounting of farm P inputs (in purchased animal feed and fertilizers) and P outputs (in milk, meat, or off-farm sales of harvested crops or other products) is needed as a means of determining potential P build-up in farm soils. When farm P inputs exceed P outputs, P surplus occurs on the farm. This leads to potential soil-P accumulations and risk of P loss in runoff, negatively impacting the quality of receiving water bodies. In this study, a combination of farm record data and a model-based approach, using the Integrated Farming System Model (IFSM), was used to estimate farm P inputs and outputs, identify root causes of farm P imbalances, and explore viable P balancing strategies. Three Vermont dairy farms with varying farm systems (grass-based organic farm, fully confined farm, and a mixed system farm with high-producing confined dairy cows and grazing heifers) were studied. These farms were found to have P surpluses ranging from 5.5 kg/ha to 18.7 kg/ha on annual basis. This study also identified critical causes of P imbalances for each farm and suggested farm specific alternative strategies needed to address the P imbalances. By balancing farm P inputs and outputs, potential accumulation of soil-P can be prevented. As a result, maximum benefits can be obtained from land treatment measures implemented to control off-field P loss without the additional concern of continuing P build-up that could reduce their effectiveness.

Phosphorus Imbalances in the Chesapeake Bay Watershed: Can Forestland and Manure Processing Facilities Be the Answers?

A mixed-integer linear programming model was formulated to minimize the cost of transport and processing of excess manure in the Chesapeake Bay watershed. The results showed that primarily poultry manure was moved out of surplus counties for land application or processing. In the base model, annual cost was more than $350 million, with the bulk of the cost arising from construction of energy facilities for poultry manure. Forestland application of poultry manure had the lowest average cost, and more forestland than agricultural land was used for manure application. The lowest cost scenario was $127 million annually when constraints were removed to expand manure application on agricultural land and allow unlimited construction of composting facilities. Such a low-cost solution could not realistically be implemented without further development of markets for compost.

Agronomic phosphorus imbalances across the world's croplands.

Increased phosphorus (P) fertilizer use and livestock production has fundamentally altered the global P cycle. We calculated spatially explicit P balances for cropland soils at 0.5° resolution based on the principal agronomic P inputs and outputs associated with production of 123 crops globally for the year 2000. Although agronomic inputs of P fertilizer (14.2 Tg of P·y(-1)) and manure (9.6 Tg of P·y(-1)) collectively exceeded P removal by harvested crops (12.3 Tg of P·y(-1)) at the global scale, P deficits covered almost 30% of the global cropland area. There was massive variation in the magnitudes of these P imbalances across most regions, particularly Europe and South America. High P fertilizer application relative to crop P use resulted in a greater proportion of the intense P surpluses (>13 kg of P·ha(-1)·y(-1)) globally than manure P application. High P fertilizer application was also typically associated with areas of relatively low P-use efficiency. Although manure was an important driver of P surpluses in some locations with high livestock densities, P deficits were common in areas producing forage crops used as livestock feed. Resolving agronomic P imbalances may be possible with more efficient use of P fertilizers and more effective recycling of manure P. Such reforms are needed to increase global agricultural productivity while maintaining or improving freshwater quality.

Phosphate toxicity: new insights into an old problem

Phosphorus is an essential nutrient required for critical biological reactions that maintain the normal homoeostatic control of the cell. This element is an important component of different cellular structures, including nucleic acids and cell membranes. Adequate phosphorus balance is vital for maintaining basic cellular functions, ranging from energy metabolism to cell signalling. In addition, many intracellular pathways utilize phosphate ions for important cellular reactions; therefore, homoeostatic control of phosphate is one of the most delicate biological regulations. Impaired phosphorus balance can affect the functionality of almost every human system, including musculoskeletal and cardiovascular systems, ultimately leading to an increase in morbidity and mortality of the affected patients. Human and experimental studies have found that delicate balance among circulating factors, like vitamin D, PTH (parathyroid hormone) and FGF23 (fibroblast growth factor 23), are essential for regulation of physiological phosphate balance. Dysregulation of these factors, either alone or in combination, can induce phosphorus imbalance. Recent studies have shown that suppression of the FGF23-klotho system can lead to hyperphosphataemia with extensive tissue damage caused by phosphate toxicity. The cause and consequences of phosphate toxicity will be briefly summarized in the present review.

Community shifts, alternative stable states, biogeochemical controls and feedbacks in eutrophic coastal lagoons: a brief overview

(1) The succession of primary producer communities in coastal lagoons is analysed in the light of the regime shift theory. Pristine coastal lagoons are considered to be dominated by extensive meadows of seagrass species, which are assumed to take advantage of nutrient supply from sediments. An increasing nutrient input is thought to favour phytoplankton and/or epiphytic micro-, macroalgae as well as opportunistic ephemeral macroalgae that coexist with seagrasses. In the latest stages of this succession, the imbalance of phosphorus to nitrogen ratio can favour macroalgal, cyanobacteria and/or picoplankton blooms, often causing dystrophy. (2) The primary causes of shifts and succession in the macrophyte community are nutrient loadings, mainly nitrogen, as well as changes in coastal hydrology or interactions between them. To some extent, in very shallow choked lagoons, benthic vegetation is mainly controlled by loading rates, while in open deep estuaries hydromorphological factors predominate. (3) External stressors/perturbations cause an amplification in benthic biogeochemical processes, e.g. wide variations in primary productivity and dark respiration, with large oscillations in oxygen and sulphide concentrations. Altered biogeochemical processes can determine positive feedbacks inducing a shift from pristine to altered macrophyte communities, which in turn amplify the perturbation until the shift becomes irreversible. (4) Macrophyte typology, organic matter composition and sedimentary geochemistry are primary factors in controlling feedbacks and shifts. For example, the sedimentary buffering capacity of iron controls sulphide and phosphates, while nitrogen cycling is mainly controlled by primary producers - microbial process interactions. (5) The alternative states which occur through the transition from pristine to modified primary producer communities can also be viewed as a sequence of stable states with different degrees of embedded information and with different ecological functions. Copyright © 2008 John Wiley & Sons, Ltd.

Outcomes of secondary hyperparathyroidism in chronic kidney disease and the direct costs of treatment.

There has been an emphasis over the last several years to identify and treat chronic kidney disease (CKD) and its complications as they evolve rather than waiting until the patient reaches end-stage renal disease (ESRD), also known as CKD stage 5. The number of patients who will be identified and prescribed therapies for complications such as secondary hyperparathyroidism (SHPT) is greater than initially proposed. To review the pathways, complications, management, and estimated treatment costs of CKD-related SHPT. An electronic literature search of MEDLINE (January 1980 through January 2007) was conducted for English-language publications using the base search term secondary hyperparathyroidism. To refine subsequent searches, the authors added Boolean operators to the following secondary and tertiary search terms: parathyroid hormone, chronic kidney disease, renal osteodystrophy, adynamic bone disease, vascular calcification, cardiovascular disease, vitamin D, vitamin D analogs, hypercalcemia, hyperphosphatemia, calcimimetics, costs, prevalence, and economics. The initial MEDLINE search produced 278 relevant articles. After refining the search terms, the authors triaged the results for English-language publications relevant to the discussion of SHPT and its complications in CKD, eliminating 149 publications. The remaining 129 publications were accepted for review. These articles represent a growing body of primarily observational evidence that demonstrates that elevated intact parathyroid hormone (PTH) levels cause deleterious physiological results across a variety of organ systems, including the cardiovascular and skeletal systems. Specific complications associated with SHPT are left ventricular hypertrophy (LVH), renal osteodystrophy (ROD), and extraskeletal calcification. Medical management of the PTH/vitamin D/calcium and phosphorus imbalances in SHPT focus on regulating PTH levels via vitamin D therapy. The class of calcimimetics is a newer treatment modality that has favorable effects on biochemical laboratory values, such as serum calcium and phosphorus levels, but current data do not show differences on hard endpoint patient-oriented outcomes compared with standard generic agents. The direct drug costs in April 2007 U.S. dollars of treating CKD-associated elevations in PTH in predialysis patients range from $8.40 per patient per week ($437 per year) for oral generic calcitriol to $88.90 per patient per week ($4,623 per year) for oral paricalcitol (expressed as 85% of average wholesale price [AWP] for brand drugs or 70% of AWP for generic drugs). The direct drug costs of treating SHPT in hemodialysis patients range from $80.20 per patient per week ($4,170 per year) for generic calcitriol (IV) to $278.46 per patient per week ($14,480 per year) for oral cinacalcet. SHPT causes skeletal and cardiovascular complications in CKD patients. Calcitriol therapy is effective in managing PTH levels, but efforts to reduce the associated hypercalcemia and hyperphosphatemia have led to the development of newer, yet more expensive, vitamin D analogs. With the lack of evidence to support comparative superior outcomes in end-organ disease among SHPT therapy alternatives, future research is still needed to clearly identify which newer agents are most competitive with the historical gold standard of calcitriol therapy.

Cardiorenal Consideration as a Risk Factor for Heart Failure

Cardiovascular disease-related factors are responsible for about 50% of the mortality in patients with both chronic kidney disease and end-stage renal disease. Therefore, it is not surprising that 30%-50% of patients with congestive heart failure also have an impaired glomerular filtration rate. This signifies a co-dependence between the kidneys and the heart. The role of anemia, microalbuminuria, calcium, and phosphorus imbalance in this cardiorenal interdependence is discussed in this article.

Ten-year effect of dolomitic lime on the nutrition, crown vigor, and growth of sugar maple

In a base-poor northern hardwood stand in Quebec, subjected to high acid deposition, sugar maple (Acer saccharum Marsh.) nutrition, growth, and crown vigor were evaluated 10 years after application of 0–50 t·ha–1 of CaMg(CO3)2 in 1994. One decade after treatment, foliar calcium and magnesium concentrations of sugar maple were still higher for treated than for control trees. The analysis of foliar nutrient indices showed that liming improved the nutrition of nitrogen and calcium, but caused imbalance of phosphorus, potassium, and magnesium. In 2004, crown dieback was much lower for limed trees (0.5%–4.5%) as compared to unlimed trees (23.7%). When compared with crown dieback before treatment, dieback of limed trees generally had decreased by 2004, while dieback of untreated maple trees increased over the 1994–2004 period. In 2004, basal area increment for limed trees was nearly double that of unlimed trees. However, no difference was detectable among trees limed at different rates. Midterm efficacy of liming in this study was demonstrated by the improvement of sugar maple calcium nutrition, crown vigor, and stem growth 10 years following treatment. This confirms the potential of liming to limit damage caused by acid deposition in base-poor and declining northern hardwood stands.

Nephrocalcinosis Caused by Dietary Calcium:Phosphorus Imbalance in Female Rats Develops Rapidly and Is Irreversible

Female rats fed the standardized AIN-76A diet develop kidney calcium deposits (nephrocalcinosis, NC). A low dietary Ca:P molar ratio is a primary factor in this disorder. The AIN-93G diet has a lower P content and higher Ca:P molar ratio and lowers the incidence of NC. To examine the early stages of NC induced by dietary Ca:P imbalance and the potential reversibility of this disorder, weanling female Sprague-Dawley rats were fed a modified AIN-93G test diet containing Ca:P at AIN-76A levels (NC-inducing diet) for 0.5-16 wk before necropsy, or were switched to AIN-93G control diet after 0.5-4 wk until necropsy at 16 wk. A dramatic increase in incidence and severity of NC was noted after 2 wk of feeding the test diet. NC was not reversible by switching to the control diet. As little as 0.5 wk of exposure to the test diet followed by 15.5 wk of consuming the control diet resulted in increased incidence and severity of NC compared with 16 wk of consuming the control diet. Short-term (as little as several days) feeding of an NC-inducing diet to female rats can lead to NC even if they are switched to an optimal diet.

Oceanic phosphorus imbalance: Magnitude of the mid‐ocean ridge flank hydrothermal sink

We present a new estimate for the crustal phosphorous sink that results from reactions among seawater, basalt, and sediment blanketing low temperature mid‐ocean ridge flank hydrothermal systems. New estimates for global hydrothermal power output, sediment thickness, and the dissolved phosphate concentrations in basement formation fluids indicate that fluid flow through ridge flanks removes 2.8 × 1010 mol P yr−1. This value is larger (130%) than the riverine dissolved flux of inorganic phosphate and is as much as 35% of the sedimentary P sink. The concordant seawater flux (2.1 × 1016 kg yr−1) is 65% of the riverine fluid flux and circulates a fluid volume equivalent to the entire ocean in about 70,000 yr. Additional sampling of seafloor springs is required to further constrain the range of calculated phosphate fluxes; nevertheless the modern phosphorus budget is clearly unbalanced with total sinks outpacing sources.