Effects of Short-Term Phosphate Loading on Aerobic Capacity under Acute Hypoxia in Cyclists: A Randomized, Placebo-Controlled, Crossover Study.

The aim of this study was to evaluate the effects of sodium phosphate (SP) supplementation on aerobic capacity in hypoxia. Twenty-four trained male cyclists received SP (50 mg·kg-1 of FFM/day) or placebo for six days in a randomized, crossover study, with a three-week washout period between supplementation phases. Before and after each supplementation phase, the subjects performed an incremental exercise test to exhaustion in hypoxia (FiO2 = 16%). Additionally, the levels of 2,3-diphosphoglycerate (2,3-DPG), hypoxia-inducible factor 1 alpha (HIF-1α), inorganic phosphate (Pi), calcium (Ca), parathyroid hormone (PTH) and acid-base balance were determined. The results showed that phosphate loading significantly increased the Pi level by 9.0%, whereas 2,3-DPG levels, hemoglobin oxygen affinity, buffering capacity and myocardial efficiency remained unchanged. The aerobic capacity in hypoxia was not improved following SP. Additionally, our data revealed high inter-individual variability in response to SP. Therefore, the participants were grouped as Responders and Non-Responders. In the Responders, a significant increase in aerobic performance in the range of 3-5% was observed. In conclusion, SP supplementation is not an ergogenic aid for aerobic capacity in hypoxia. However, in certain individuals, some benefits can be expected, but mainly in athletes with less training-induced central and/or peripheral adaptation.

Acute Effects of an Inorganic Phosphorus Additive on Mineral Metabolism and Cardiometabolic Risk Factors in Healthy Subjects.

CONTEXT: Hyperphosphatemia and high levels of fibroblast growth factor 23 (FGF23) are risk factors for cardiovascular events in patients with chronic kidney diseases. However, the impact of an inorganic phosphorus additive in healthy people is largely unknown. OBJECTIVE: We aimed to investigate the acute effect of excessive dietary phosphorus administered as sodium dihydrogen phosphate on the postprandial levels of Pi and FGF23 and the response to food. METHODS: This study was a double-blind placebo-controlled crossover study with 29 healthy male and female participants from the general community who were administered a single dose of either 700 mg phosphorus (NaH2PO4) or a sodium-adjusted placebo in combination with a test meal. Postprandial plasma levels of Pi and FGF23 were measured. RESULTS: Compared with placebo, oral phosphorus increased the plasma Pi level, which remained elevated during the ensuing 8 hours (at 480 minutes: 1.31 vs 1.16 mmol/l; P < 0.001), increased urinary Pi (iAUC0-480 789 vs 95 mmol/mmol; P < 0.001), reduced tubular Pi reabsorption (iAUC0-480 -31.5 vs -6.2; P < 0.001), decreased urinary calcium (iAUC0-240 30.6 vs 53.0 mmol/mmol; P = 0.009), and stimulated the release of parathyroid hormone (iAUC0-480 2212 vs 768 ng/l; P < 0.001). However, the FGF23 levels did not change. Postprandial levels of glucose, insulin, and lipids were not substantially affected by phosphorus vs placebo. CONCLUSION: An oral phosphorus load can induce elevated postprandial levels of circulating Pi for hours in healthy subjects, despite rapid homeostatic counterreactions. FGF23 levels and the postprandial response to food were not affected.

Phosphorothioate-DNA bacterial diet reduces the ROS levels in C. elegans while improving locomotion and longevity.

DNA phosphorothioation (PT) is widely distributed in the human gut microbiome. In this work, PT-diet effect on nematodes was studied with PT-bioengineering bacteria. We found that the ROS level decreased by about 20-50% and the age-related lipofuscin accumulation was reduced by 15-25%. Moreover, the PT-feeding worms were more active at all life periods, and more resistant to acute stressors. Intriguingly, their lifespans were prolonged by ~21.7%. Comparative RNA-seq analysis indicated that many gene expressions were dramatically regulated by PT-diet, such as cysteine-rich protein (scl-11/12/13), sulfur-related enzyme (cpr-2), longevity gene (jnk-1) and stress response (sod-3/5, gps-5/6, gst-18/20, hsp-12.8). Both the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that neuroactivity pathways were upregulated, while phosphoryl transfer and DNA-repair pathways were down-regulated in good-appetite young worms. The findings pave the way for pro-longevity of multicellular organisms by PT-bacterial interference.

An Evaluation of Phosphate Buffer Saline as an Alternative Liquid-Based Medium for HPV DNA Detection.

OBJECTIVE: HPV detection has been proposed as part of the co-testing which improves the sensitivity of cervical screening. However, the commercially liquid-based medium adds cost in low-resource areas. This study aimed to evaluate the performance of ice-cold phosphate buffer saline (PBS) for HPV detection. METHODS: HPV DNA from SiHa cells (with 1-2 copies of HPV16 per cell) preserved in ice-cold PBS or PreserveCyt solution at different time points (24, 36, 48, 72, 120 and 168 h) was tested in triplicate using Cobas 4800. The threshold cycle (Ct) values of both solutions were compared. An estimated false negative rate of PBS was also assessed by using the difference in Ct values between both solutions (∆Ct) and Ct values of HPV16-positive PreserveCyt clinical samples (Ctsample) at corresponding time points. Samples with a (Ctsample+∆Ct) value > 40.5 (the cutoff of HPV16 DNA by Cobas 4800) were considered as false negativity. RESULTS: The Ct values of HPV16 DNA of SiHa cells collected in PBS were higher than PreserveCyt ranging from 0.43 to 2.36 cycles depending on incubation times. There was no significant difference at 24, 72, 120, and 168 h.  However, the Ct values were statistically significantly higher for PBS than PreserveCyt at 36 h (31.00 vs 29.26), and 48 h (31.06 vs 28.70). A retrospective analysis in 47 clinical PreserveCyt collected samples that were positive for HPV16 DNA found that 1 case (2%) would become negative if collected in ice-cold PBS. CONCLUSIONS: The PBS might be an alternative collecting medium for HPV detection in the low-resource areas. Further evaluations are warranted.

Association between phosphate and long-term outcome in CAD patients underwent coronary intervention.

Phosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization (HHF). The key secondary outcome was MACE. There was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1 mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE + HHF (HR: 1.12, 95% CI: 1.05-1.21): CV death (HR: 1.37, 95% CI: 1.22-1.55) and HHF (HR: 1.12, 95% CI: 1.02-1.23). Subgroup analyses showed more prominent association between phosphate and MACE + HHF in male, age > 65, bare-metal stents (BMSs), LVEF < 50%, eGFR < 60, LDL > 70 mg/dL, and emergent PCI. Phosphate has a significant association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function.

Ionic homeostasis, acid-base balance and the risk of citrate accumulation in patients after cardiovascular surgery treated with continuous veno-venous haemofiltration with post-dilution regional citrate anticoagulation - An observational case-control study.

BACKGROUND: Patients after cardiovascular surgery, requiring renal replacement therapy, can benefit from adequate non-heparin circuit anticoagulation. Simplified regional citrate anticoagulation (RCA) protocol proposes the use of citric acid dextrose formula A (ACD-A) during post-dilutional continuous veno-venous hemofiltration (CVVH) with standard bicarbonate buffered calcium containing replacement solution. Citrate accumulation diagnosed upon total to ionized calcium ratio (tCa/iCa) and low ionized calcium (iCa) are considered as the biggest risks related to regional citrate accumulation. METHODS: This prospective observational case-control study evaluated electrolyte and acid-base homeostasis in cardiovascular surgery patients treated with post-dilution CVVH with a simplified RCA protocol with ACD-A. In total, 50 consecutive cardiovascular surgery patients were evaluated. Base excess, pH, bicarbonate, lactate, Na+, Cl-, Mg++, and inorganic phosphate concentrations, the total to ionized calcium ratio (tCa/iCa), and high anion gap metabolic acidosis were assessed during haemofiltration treatment in survivors and non-survivors. RESULTS: Thirty-three (66%) patients died. The therapies were very well balanced in sodium and chloride homeostasis. The lactate concentration and anion gap decreased during CVVH sessions lasting longer than 72 hours, but no inter-group difference was observed. The tCa/iCa ratio exceeded 4.5% and was significantly higher in non-survivors (p=0.037). Initial lactate concentration did not correlate with tCa/iCa ratio during haemofiltration. Magnesium and phosphate concentrations decreased and additional supplementation with magnesium was necessary. The magnesium concentration was lower in the non-survivors. CONCLUSIONS: The incidence of citrate accumulation exceeded 4% and was significantly higher in non-survivors. Supplementation with magnesium and phosphate ions is needed in CVVH with RCA.

Genome accessibility dynamics in response to phosphate limitation is controlled by the PHR1 family of transcription factors in Arabidopsis.

As phosphorus is one of the most limiting nutrients in many natural and agricultural ecosystems, plants have evolved strategies that cope with its scarcity. Genetic approaches have facilitated the identification of several molecular elements that regulate the phosphate (Pi) starvation response (PSR) of plants, including the master regulator of the transcriptional response to phosphate starvation PHOSPHATE STARVATION RESPONSE1 (PHR1). However, the chromatin modifications underlying the plant transcriptional response to phosphate scarcity remain largely unknown. Here, we present a detailed analysis of changes in chromatin accessibility during phosphate starvation in Arabidopsis thaliana root cells. Root cells undergo a genome-wide remodeling of chromatin accessibility in response to Pi starvation that is often associated with changes in the transcription of neighboring genes. Analysis of chromatin accessibility in the phr1 phl2 double mutant revealed that the transcription factors PHR1 and PHL2 play a key role in remodeling chromatin accessibility in response to Pi limitation. We also discovered that PHR1 and PHL2 play an important role in determining chromatin accessibility and the associated transcription of many genes under optimal Pi conditions, including genes involved in the PSR. We propose that a set of transcription factors directly activated by PHR1 in Pi-starved root cells trigger a second wave of epigenetic changes required for the transcriptional activation of the complete set of low-Pi-responsive genes.

Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression.

The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.

Asymmetric physiological response of a reef-building coral to pulsed versus continuous addition of inorganic nutrients.

Coral reefs, especially those located near-shore, are increasingly exposed to anthropogenic, eutrophic conditions that are often chronic. Yet, corals under unperturbed conditions may frequently receive natural and usually temporary nutrient supplementation through biological sources such as fishes. We compared physiological parameters indicative of long- and short-term coral health (day and night calcification, fragment surface area, productivity, energy reserves, and tissue stoichiometry) under continuous and temporary nutrient enrichment. The symbiotic coral Acropora intermedia was grown for 7 weeks under continuously elevated (press) levels of ammonium (14 µmol L-1) and phosphate (10 µmol L-1) as separate and combined treatments, to discern the individual and interactive nutrient effects. Another treatment exposed A. intermedia twice-daily to an ammonium and phosphate pulse of the same concentrations as the press treatments to simulate natural biotic supplementation. Press exposure to elevated ammonium or phosphate produced mixed effects on physiological responses, with little interaction between the nutrients in the combined treatment. Overall, corals under press exposure transitioned resources away from calcification. However, exposure to nutrient pulses often enhanced physiological responses. Our findings indicate that while continuous nutrient enrichment may pose a threat to coral health, episodic nutrient pulses that resemble natural nutrient supplementation may significantly benefit coral health and physiology.

The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis.

BACKGROUND & AIMS: Heavy alcohol consumption is a common cause of acute pancreatitis; however, alcohol abuse does not always result in clinical pancreatitis. As a consequence, the factors responsible for alcohol-induced pancreatitis are not well understood. In experimental animals, it has been difficult to produce pancreatitis with alcohol. Clinically, alcohol use predisposes to hypophosphatemia, and hypophosphatemia has been observed in some patients with acute pancreatitis. Because of abundant protein synthesis, the pancreas has high metabolic demands, and reduced mitochondrial function leads to organelle dysfunction and pancreatitis. We proposed, therefore, that phosphate deficiency might limit adenosine triphosphate synthesis and thereby contribute to alcohol-induced pancreatitis. METHODS: Mice were fed a low-phosphate diet (LPD) before orogastric administration of ethanol. Direct effects of phosphate and ethanol were evaluated in vitro in isolated mouse pancreatic acini. RESULTS: LPD reduced serum phosphate levels. Intragastric administration of ethanol to animals maintained on an LPD caused severe pancreatitis that was ameliorated by phosphate repletion. In pancreatic acinar cells, low-phosphate conditions increased susceptibility to ethanol-induced cellular dysfunction through decreased bioenergetic stores, specifically affecting total cellular adenosine triphosphate and mitochondrial function. Phosphate supplementation prevented ethanol-associated cellular injury. CONCLUSIONS: Phosphate status plays a critical role in predisposition to and protection from alcohol-induced acinar cell dysfunction and the development of acute alcohol-induced pancreatitis. This finding may explain why pancreatitis develops in only some individuals with heavy alcohol use and suggests a potential novel therapeutic approach to pancreatitis. Finally, an LPD plus ethanol provides a new model for studying alcohol-associated pancreatic injury.

Water-soluble derivatives of evodiamine: Discovery of evodiamine-10-phosphate as an orally active antitumor lead compound.

10-Hydroxyevodiamine is a multitargeting antitumor lead compound with excellent in vitro activity. However, its in vivo antitumor potency is rather limited, which has hampered its further clinical development. To overcome this obstacle, a series of novel water-soluble derivatives of 10-hydroxyevodiamine were designed and synthesized. Most of them exhibited good to excellent antitumor activities against several cancer cell lines. In particular, phosphate derivative 9 was orally active and showed improved in vivo antitumor efficacy in HCT116 xenograft models. Further antitumor mechanism studies indicated that compound 9 acted by triple Top1/Top2/tubulin inhibition and induced apoptosis with G2/M cell cycle arrest. Taken together, this study extended the structure-activity relationship of evodiamine and identified phosphate derivative 9 as a promising antitumor lead compound.

A Reduced Dose Whole Virion Aluminum Adjuvanted Seasonal Influenza Vaccine Is Immunogenic, Safe, and Well Tolerated in Pediatric Patients.

BACKGROUND: Data suggest that pediatric patients might react differently to influenza vaccination, both in terms of immunity and side effects. We have recently shown that using a whole virion vaccine with aluminum phosphate adjuvants, reduced dose vaccines containing 6 µg of viral hemagglutinin (HA) per strain are immunogenic, and well tolerated in adult and elderly patients. Here we show the results of a multicenter clinical trial of pediatric patients, using reduced doses of a new, whole virion, aluminum phosphate adjuvanted vaccine (FluArt, Budapest, Hungary). METHODS: A total of 120 healthy volunteers were included in two age groups (3-11 years, receiving 3 µg of HA per strain, and 12-18 years, receiving 6 µg of HA per strain). We used hemagglutination inhibition testing to assess immunogenicity, based on EMA and FDA licensing criteria, including post/pre-vaccination geometric mean titer ratios, seroconversion and seropositivity rates. Safety and tolerability were assessed using CHMP guidelines. RESULTS: All subjects entered the study and were vaccinated (ITT population). All 120 subjects attended the control visit on Day 21 (PP population). All immunogenicity licensing criteria were met in both age groups for all three vaccine virus strains. No serious adverse events were detected and the vaccine was well tolerated by both age groups. DISCUSSION: Using a whole virion vaccine and aluminum phosphate adjuvants, a reduction in the amount of the viral hemmaglutinin is possible while maintaining immunogenicity, safety and tolerability in pediatric and adolescent patients.

Acylation of non-specific phospholipase C4 determines its function in plant response to phosphate deficiency.

Non-specific phospholipase C (NPC) is involved in plant growth, development and stress responses. To elucidate the mechanism by which NPCs mediate cellular functions, here we show that NPC4 is S-acylated at the C terminus and that acylation determines its plasma membrane (PM) association and function. The acylation of NPC4 was detected using NPC4 isolated from Arabidopsis and reconstituted in vitro. The C-terminal Cys-533 was identified as the S-acylation residue, and the mutation of Cys-533 to Ala-533 in NPC4 (NPC4C533A ) led to the loss of S-acylation and membrane association of NPC4. The knockout of NPC4 impeded the phosphate deficiency-induced decrease of the phosphosphingolipid glycosyl inositol phosphoryl ceramide (GIPC), but introducing NPC4C533A to npc4-1 failed to complement this defect, thereby supporting the hypothesis that the non-acylated NPC4C533A fails to hydrolyze GIPC during phosphate deprivation. Moreover, NPC4C533A failed to complement the primary root growth in npc4-1 under stress. In addition, NPC4 in Brassica napus was S-acylated and mutation of the S-acylating cysteine residue of BnaC01.NPC4 led to the loss of S-acylation and its membrane association. Together, our results reveal that S-acylation of NPC4 in the C terminus is conserved and required for its membrane association, phosphosphingolipid hydrolysis and function in plant stress responses.

Refractory hypophosphatemia following ferric carboxymaltose administration.

Hypophosphatemia is a rare side effect of intravenous iron replacement. Urinary phosphate wasting due to increased FGF23 is the most likely mechanism. Here, we present a case of intractable hypophosphatemia in a 32-year-old female patient with history of ulcerative colitis (UC), who was primarily hospitalized due to UC flare-up. Her urinary fractional excretion of phosphate was inappropriately elevated at 70%. A careful history revealed that she had been treated with ferric carboxymaltose 2 weeks prior to hospitalization, leading to a diagnosis of iron-induced hypophosphatemia. She was treated with 5 weeks of intravenous sodium phosphate since she did not tolerate oral supplementation. In conclusion, clinicians should be aware of iron-induced hypophosphatemia and be cautious when prescribing intravenous iron.

Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine.

In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.A cross-sectional study was performed in 71 patients affected by metabolic syndrome with CKD (stages 2-3) with normal serum P concentration. A 3-day dietary survey was performed to estimate the average daily amount and the source of P ingested. The daily intake ofPwas1086.5 ± 361.3mg/day; 64% contained in animal proteins, 22% in vegetable proteins, and 14% as inorganic P. The total amount of P ingested did not correlate with daily phosphaturia, but it did correlate with the P/UUN ratio (p < 0.018). Patients with the highest tertile of the P/UUN ratio >71.1 mg/g presented more abundant inorganic P intake (p < 0.038).The P/UUN ratio is suggested to be a marker of inorganic P intake. This finding might be useful in clinical practices to identify the source of dietary P and to make personalized dietary recommendations directed to reduce inorganic P intake.

Investigation of the transforming growth factor-beta 1 signalling pathway as a possible link between hyperphosphataemia and renal fibrosis in feline chronic kidney disease.

Chronic kidney disease (CKD) is common in geriatric cats, and is characterised in the majority of cases by tubulointerstitial inflammation and fibrosis. Hyperphosphataemia is a frequent complication of CKD and is independently associated with severity of renal fibrosis and disease progression. Transforming growth factor-beta 1 (TGF-ß1) signalling is thought to be a convergent pathway which mediates the progression of renal fibrosis in CKD. The aims of this study were to explore the interaction between increased extracellular phosphate and the TGF-ß1 signalling pathway by investigating: (a) the effect of a commercially available, phosphate-restricted, diet on urinary TGF-ß1 excretion in cats with CKD; and (b) the role of increased extracellular phosphate in regulating proliferation, apoptosis, and expression of genes related to TGF-ß1 signalling and extracellular matrix (ECM) production in feline proximal tubular epithelial cells (FPTEC) and cortical fibroblasts from cats with azotaemic CKD (CKD-FCF). The dietary intervention study revealed no effect of dietary phosphate restriction on urinary active TGF-ß1 excretion after 4-8 weeks (P=0.98), despite significantly decreasing serum phosphate (P<0.001). There was no effect of increased growth media phosphate concentration (from 0.95mM to 2mM and 3.5mM) on proliferation (P=0.99) and apoptotic activity in FPTEC (P=0.22), or expression of genes related to ECM production and the TGF-ß1 signalling pathway in FPTEC and CKD-FCF (P>0.05). These findings suggest the beneficial effects of dietary phosphate restriction on progression of feline CKD may not occur through modulation of renal TGF-ß1 production, and do not support a direct pro-fibrotic effect of increased extracellular phosphate on feline renal cells.

[Neonatal parenteral nutrition formulation: where are we?] / Formulación de nutrición parenteral neonatal: ¿dónde estamos?

INTRODUCTION: Introduction: the introduction of parenteral nutrition in preterm infants has meant a major advance in their prognosis, being the last few years very fruitful in terms of publication of guidelines in this area. Objectives: to know the formulation and preparation procedures of neonatal parenteral nutrition (NPN) in Spanish hospitals. Methods: a multi-centre survey was conducted in Pharmacy Services on the aforementioned processes. Results: fifty-five hospitals met inclusion criteria. Electronic prescription systems were use by 51 %, 65.5 % always formulated individually, while 34.4 % had predesigned formulas. Tricameral preparations were used by 13.0 %. In 52.7 % of cases, first day nutrition was prepared on demand, starting before 8 hours of life in 88.1 % of cases. Inorganic phosphate was the first option in 10.4 %, vitamins, trace elements and zinc were added daily in 92.7 %, 90.9 % and 70.9 % of cases, respectively. NPN including lipids in the same bag was formulated by 45.4 % of the hospitals, compared to 34.5 % where it was administered separately in all cases. In 50.9 % of hospitals they never added heparin to their NPN. The 89.1 % used photoprotected bags. The stability of the admixture varied from 24 hours to 15 days. Conclusion: the elaboration of the PPN in Spain is subject to great variability. There is controversy regarding the use of heparin and ternary mixtures, which is reflected in the variability of clinical practice.

INTRODUCCIÓN: .Introducción: la instauración de nutrición parenteral al prematuro ha supuesto un importante avance en su pronóstico. Los últimos años han sido muy fructíferos en cuanto a la publicación de guías en este ámbito. Objetivos: conocer los procedimientos de formulación y elaboración de las nutriciones parenterales neonatales (NPN) en los hospitales españoles. Métodos: se llevó a cabo una encuesta multicéntrica dirigida a los servicios de farmacia sobre los procesos anteriormente citados. Resultados: 55 hospitales cumplieron criterios de inclusión. El 51 % disponía de sistemas informáticos de prescripción, y el 65,5 % formulaba siempre de forma individualizada, mientras que el 34,4 % disponía de fórmulas prediseñadas. Los preparados tricamerales eran utilizados por el 13,0 %. En el 52,7 % de los casos se preparaban las nutriciones de primer día bajo demanda, y ésta se iniciaba antes de las 8 horas de vida en un 88,1 % de los casos. El fosfato inorgánico era la primera opción en un 10,4 %. Se añadían diariamente vitaminas, oligoelementos y zinc en el 92,7 %, 90,9 % y 70,9 % de los casos, respectivamente. El 45,4 % de los hospitales elaboraba siempre las NPPN incluyendo los lípidos en la misma bolsa, frente al 34,5 % en los que estos se administraban por separado en todos los casos. El 50,9 % de los hospitales nunca añadía heparina a sus nutriciones. Las bolsas fotoprotectoras eran utilizadas por un 89,1 %. La estabilidad de las nutriciones variaba desde 24 horas a 15 días. Conclusiones: la elaboración de la NPN en España está sujeta a gran variabilidad. Existe controversia respecto al uso de heparina y mezclas ternarias, reflejada en la variabilidad de la práctica clínica.

Modulating phosphate consumption, a novel therapeutic approach for the control of cancer cell proliferation and tumorigenesis.

Phosphorus, often in the form of inorganic phosphate (Pi), is critical to cellular function on many levels; it is required as an integral component of kinase signaling, in the formation and function of DNA and lipids, and energy metabolism in the form of ATP. Accordingly, crucial aspects of cell mitosis - such as DNA synthesis and ATP energy generation - elevate the cellular requirement for Pi, with rapidly dividing cells consuming increased levels. Mechanisms to sense, respond, acquire, accumulate, and potentially seek Pi have evolved to support highly proliferative cellular states such as injury and malignant transformation. As such, manipulating Pi availability to target rapidly dividing cells presents a novel strategy to reduce or prevent unrestrained cell growth. Currently, limited knowledge exists regarding how modulating Pi consumption by pre-cancerous cells might influence the initiation of aberrant growth during malignant transformation, and if reducing the bioavailability or suppressing Pi consumption by malignant cells could alter tumorigenesis. The concept of targeting Pi-regulated pathways and/or consumption by pre-cancerous or tumor cells represents a novel approach to cancer prevention and control, although current data remains insufficient as to rigorously assess the therapeutic value and physiological relevance of this strategy. With this review, we present a critical evaluation of the paradox of how an element critical to essential cellular functions can, when available in excess, influence and promote a cancer phenotype. Further, we conjecture how Pi manipulation could be utilized as a therapeutic intervention, either systemically or at the cell level, to ultimately suppress or treat cancer initiation and/or progression.