Long-term impact of legume-inclusive diversification and nutrient management practices on phosphorus dynamics in alkaline Fluvisol.

An insight into the dynamics of soil phosphorus (P) pools with long-term cropping/management practices would help in designing efficient and sustainable management module(s). The study aimed to investigate the long-term impact of diversified rice-based rotations and variable nutrient management practices on the dynamic composition of P pools and their influence on systems' base-crop productivity in an alkaline soil of Indo-Gangetic plain (Fluvisol). Treatments consisted of four rotations [rice-wheat (R-W), rice-wheat-mungbean (R-W-Mb), rice-wheat-rice-chickpea (R-W-R-C), rice-chickpea (R-C)] each with three nutrient treatments [control (CT), integrated nutrient management (INM), sole-chemical fertilizers (CF)]. Notably, R-C exhibited higher levels of bioavailable-P (soluble-P, Ca2-P, labile-Po), particularly in subsurface soil depth (0.2-0.4 m) compared to other rotations. Likewise, the inclusion of chickpea every alternate year (R-W-R-C) resulted in higher Ca2-P (40%), labile-Pi (15%), labile-Po (11%), and moderately labile Po (8%) compared to R-W rotation demonstrating an increased significance of chickpea in maintaining a favorable soil P regime in alkaline soil. Both R-C and R-W-R-C reduced the surface-to-subsurface depth ratio (SSBR) of soluble-P and Ca2-P while increasing the ratio for microbial biomass P. Even with a suboptimal fertilizer-P rate, INM significantly increased soluble-P (4-33%), labile-Po (13-17%), microbial biomass P (10-26%), moderately labile-Po (4-17%) compared to CF and exhibited higher SSBR values. Correlation analysis demonstrated the substantial influence of very-labile carbon, microbial and phosphatase activities on P availability. The treatment-induced changes in labile-P pools significantly influenced rice (base-crop) yields. In conclusion, chickpea-inclusive diversification and INM could be a sustainable approach to enhance P bioavailability and crop productivity in tropical rice soils.

Long-term impact of pulses and organic amendments inclusion in cropping system on soil physical and chemical properties.

Mono-cropping of maize-wheat, mechanical disintegration of soils, and continuous chemical fertilization have deteriorated soil health in the Indo-Gangetic Plains. We studied the long-term impact of pulse-based cropping systems with integrated nutrient management on soil physical and chemical properties and yield sustainability. We evaluated four different cropping systems: (1) maize-wheat (M-W), (2) maize-wheat-mungbean (M-W-Mb), (3) maize-wheat-maize-chickpea (M-W-M-C), (4) pigeonpea-wheat (P-W) each with three degrees of soil fertilization techniques: (1) unfertilized control (CT), (2) inorganic fertilization (RDF), and (3) integrated nutrient management (INM). The field experiment was undertaken in a split-plot design with three replications each year with a fixed layout. P-W and M-W-Mb systems enhanced soil properties such as volume expansion by 9-25% and porosity by 7-9% (p < 0.05) more than M-W, respectively. P-W and M-W-Mb increased soil organic carbon by 25-42% and 12-50% over M-W (RDF). P-W system enhanced water holding capacity and gravimetric moisture content by 10 and 11% (p < 0.05) than M-W. Pulse-based systems (P-W and M-W-Mb) had higher available nitrogen (8-11%), phosphorus (42-73%), and potassium (8-12%) over M-W (p < 0.05). M-W-Mb increased 26% maize yield and 21% wheat yield over M-W (p < 0.05) at the thirteenth crop cycle. P-W system had a higher sustainable yield index (p < 0.05) of wheat over the M-W. Thus, pulse inclusion in the cropping system in combination with INM can enhance physical and chemical properties vis-à-vis sustainable yield index over the cereal-cereal system.

Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation.

Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p ≤ 0.001]. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2-4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 [95% CI: 1.06-3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.

Expansion of hay production and marketing in Brazil.

In the last decade, advances in Brazilian hay production showed that the country has the potential to produce bulky dehydrated fodder. For many years, the Brazilian hay production scientific knowledge had been based on temperate climate species, even though the best hay material are tropical grasses, as Tifton 85 Bermudagrass. Researches that focused on the comprehension of yield systems, biochemical processes, physiology, composition, and nutritional quality of tropical species under dehydration and conservation have become important to hay yield in Brazil. Therefore, this literature review aimed to discuss the hay research contribution in tropical conditions and its reflex on the production and commercialization of hay in Brazil. This review was based on database research with key-words defined in a period between 1960 and 2021, which resulted in 33 articles. Each article had the strengths and weaknesses, opportunities, and threats classified according to the SWOT matrix. Articles related to the haymaking system with tropical forage and the effects on nutritional value, sanitary quality, and factors that influence the dehydration period in the field and storage were listed in this paper. Based on the literature, the conclusion is that Brazil has elevated hay yield potential with high nutritional and sanitary quality of tropical species due to the weather conditions that allow fast dehydration and, also, the availability of residual wastewater as fertilization and machinery appropriated. Brazilian haymaking and commercialization are in an expansion process with economic return as national and international trade. Further challenges: to obtain a constant annual hay supply and the transport viability to markets distant from the production center.

Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.

AIMS: Carboplatin dosage is calculated by using the estimated glomerular filtration rate (GFR) to achieve a target plasma area under the plasma concentration-time curve (AUC). The aims of the present study were to investigate factors that influence the pharmacokinetics of carboplatin in children with high-risk neuroblastoma, and whether target exposures for carboplatin were achieved using current treatment protocols. METHODS: Data on children receiving high-dose carboplatin, etoposide and melphalan for neuroblastoma were obtained from two study sites [European International Society for Paediatric Oncology (SIOP) Neuroblastoma study, Children's Hospital at Westmead; n = 51]. A population pharmacokinetic model was built for carboplatin to evaluate various dosing formulas. The pharmacokinetics of etoposide and melphalan was also investigated. The final model was used to simulate whether target carboplatin AUC (16.4 mg ml-1 ·min) would be achieved using the paediatric Newell formula, modified Calvert formula and weight-based dosing. RESULTS: Allometric weight was the only significant, independent covariate for the pharmacokinetic parameters of carboplatin, etoposide and melphalan. The paediatric Newell formula and modified Calvert formula were suitable for achieving the target AUC of carboplatin for children with a GFR <100 ml min-1 1.73 m-2 but not for those with a GFR ≥100 ml min-1 1.73 m-2 . A weight-based dosing regimen of 50 mg kg-1 achieved the target AUC more consistently than the other formulas, regardless of renal function. CONCLUSIONS: GFR did not appear to influence the pharmacokinetics of carboplatin after adjusting pharmacokinetic parameters for weight. This model-based approach validates the use of weight-based dosing as an appropriate alternative for carboplatin in children with either mild renal impairment or normal renal function.

6-Hydroxydopamine and lipopolysaccharides induced DNA damage in astrocytes: involvement of nitric oxide and mitochondria.

The present study was conducted to investigate the effect of the neurotoxins 6-hydroxydopamine and lipopolysaccharide on astrocytes. Rat astrocyte C6 cells were treated with different concentration of 6-hydroxydopamine (6-OHDA)/lipopolysaccharides (LPS) for 24 h. Both neurotoxins significantly decreased the viability of astrocytes, augmented the expression of inducible nitric oxide synthase (iNOS) and the astrocyte marker--glial fibrillar acidic protein. A significantly decreased mitochondrial dehydrogenase activity, mitochondrial membrane potential, augmented reactive oxygen species (ROS) level, caspase-3 mRNA level, chromatin condensation and DNA damage was observed in 6-OHDA/LPS treated astroglial cells. 6-OHDA/LPS treatment also caused the significantly increased expression of iNOS and nitrite level. Findings showed that 6-OHDA/LPS treatment caused mitochondrial dysfunction mediated death of astrocytes, which significantly involve the nitric oxide. Since we have observed significantly increased level of iNOS along with mitochondrial impairment and apoptotic cell death in astrocytes, therefore to validate the role of iNOS, the cells were co-treated with iNOS inhibitor aminoguanidine (AG, 100 µM). Co-treatment of AG significantly attenuated the 6-OHDA/LPS induced cell death, mitochondrial activity, augmented ROS level, chromatin condensation and DNA damage. GFAP and caspase-3 expression were also inhibited with co-treatment of AG, although the extent of inhibition was different in both experimental sets. In conclusion, the findings showed that iNOS mediated increased level of nitric oxide acts as a key regulatory molecule in 6-OHDA/LPS induced mitochondrial dysfunction, DNA damage and apoptotic death of astrocytes.

Promising Role of Melatonin as Neuroprotectant in Neurodegenerative Pathology.

Melatonin treatment showed a potent neuroprotective action in experimental models and in clinical studies. However, the entire disease prevention is not observed with melatonin treatment. Therefore, findings have suggested its future use in combination therapies for neurological diseases. Several studies have showed its free radical scavenging, antioxidant property, antiapoptotic activity, and its action towards enhanced mitochondrial function. It has direct and indirect effects on mitochondrial functions. Neurodegenerative disease pathology includes the impaired mitochondrial functions and apoptotic death of neurons due to energy crisis which could be prevented with antiapoptotic activity of melatonin. However, for the therapeutic use of melatonin, researchers also need to pay attention towards the various intermediary events taking place in apoptotic death of neurons during disease pathology. Age-related neurological diseases include the decreased level of melatonin in neuronal death. Therefore, it is worthwhile to discuss about the different functions of melatonin in aspect of its antioxidative property, its role in the enhancement of mitochondrial function, and its antiapoptotic attributes. This review summarizes the reports to date showing the potent role of melatonin in experimental models and clinical trials and discussing the employment of melatonin as future potent neuroprotective agent.

Not too little, not too much-just right! (Better ways to give high dose melphalan).

Of the 13 286 autologous haematopoietic cell transplant procedures reported in the US in 2010-2012 for plasma cell disorders, 10 557 used single agent, high-dose melphalan. Despite 30 years of clinical and pharmacokinetic (PK) experience with high-dose melphalan, and its continuing central role as cytoreductive therapy for large numbers of patients with myeloma, the pharmacodynamics and pharmacogenomics of melphalan are still in their infancy. The addition of protectant agents such as amifostine and palifermin allows dose escalation to 280 mg/m(2), but at these doses it is cardiac, rather than gut, toxicity that is dose-limiting. Although combination with additional alkylating agents is feasible, the additional TRM may not be justified when so many post-consolidation therapies are available for myeloma patients. Current research should optimise the delivery of this single-agent chemotherapy. This includes the use of newer formulations and real-time PKs. These strategies may allow a safe and effective platform for adding synergistic novel therapies and provide a window of lymphodepletion for the addition of immunotherapies.

Okadaic acid-induced Tau phosphorylation in rat brain: role of NMDA receptor.

Okadaic acid (OKA) is a potent inhibitor of protein phosphatases 1/2A (PP2A). Inhibition of PP2A leads to hyperphosphorylation of Tau protein. Hyperphosphorylated Tau protein is present in intraneuronal neurofibrillary tangles a characteristic feature of neuropathology of Alzheimer's disease. Intracerebroventricular (ICV) administration of OKA causes neurotoxicity, which is associated with increased intracellular Ca(2+) level, oxidative stress, and mitochondrial dysfunction in the brain areas. The present study explored Tau phosphorylation in OKA-treated rats in relation to memory function, PP2A activity, intracellular Ca(2+), glycogen synthase kinase-3ß (GSK-3ß) and N-methyl-d-aspartate (NMDA) receptor after 13days of OKA (200ng, ICV) administration in rats, memory was found impaired in the water maze test. OKA-induced memory-impaired rats showed increased mRNA and protein expression of Tau, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), Calpain and GSK3ß in the hippocampus and cerebral cortex. On the other hand, mRNA expression and activity of PP2A was reduced in these brain areas. OKA treatment also, resulted in decrease in mRNA expression of C and N terminals of Tau. Treatment with NMDA antagonist, MK801 (0.05mg/kg, i.p.) for 13days significantly prevented OKA-induced changes in the expression of PP2A, Tau, GSK3ß, CaMKII and Calpain. Further, daily administration of anticholinergic drug, donepezil (5mg/kg, p.o.), and the NMDA receptor antagonist, memantine (10mg/kg, p.o.) initiated after OKA administration for 13days significantly attenuated OKA-induced variation in Tau, Tau-C terminal, Tau-N terminal CaMKII, Calpain, PP2A and GSK3ß. These results infer that NMDA antagonist MK801 and memantine are effective against OKA-induced neurotoxicity. Therefore, the present study clearly indicates the involvement of NMDA receptor in OKA (ICV)-induced Tau hyperphosphorylation.

Rotenone-induced neurotoxicity in rat brain areas: a study on neuronal and neuronal supportive cells.

The present study was conducted to correlate rotenone-induced neurotoxicity with cellular and molecular modifications in neuronal and neuronal supportive cells in rat brain regions. Rotenone was administered (3, 6 and 12 µg/µl) intranigrally in adult male Sprague-Dawley rats. After the 7th day of rotenone treatment, specific protein markers for neuronal cells - tyrosine hydroxylase (TH), astroglial cells - glial fibrillary acidic protein (GFAP), microglial cells - CD11b/c, and Iba-1 were evaluated by immunoblotting and immunofluorescence in the striatum (STR) and mid brain (MB). Apoptotic cell death was assessed by caspase-3 gene expression. Higher doses of rotenone significantly lowered TH protein levels and elevated Iba-1 levels in MB. All the doses of rotenone significantly increased GFAP and CD11b/c protein in the MB. In STR, rotenone elevated GFAP levels but did not affect TH, CD11b/c and Iba-1 protein levels. Caspase-3 expression was increased significantly by all the doses of rotenone in MB but in STR only by higher doses (6 and 12 µg). It may be suggested that astroglial activation and apoptosis play an important role in rotenone-induced neurotoxicity. MB appeared as more sensitive than STR toward rotenone-induced cell toxicity. The astroglial cells emerged as more susceptible than neuronal and microglial cells to rotenone in STR.

Erratum to: Elephants also like coffee: Trends and drivers of human-elephant conflicts in coffee agroforestry landscapes of Kodagu, Western Ghats, India.

Kodagu district produces 2% of the world's coffee, in complex, multistoried agroforestry systems. The forests of the district harbour a large population of the Asian elephant (Elephas maximus). The combined effects of high elephant density and major landscape changes due to the expansion of coffee cultivation are the cause of human-elephant conflicts (HEC). Mitigation strategies, including electric fences and compensation schemes implemented by the Forest Department have met with limited success. Building on previous studies in the area, we assessed current spatial and temporal trends of conflict, analysed local stakeholders' perceptions and identified factors driving elephants into the estates. Our study, initiated in May 2007, shows that the intensity of HEC has increased over the last 10 years, exhibiting new seasonal patterns. Conflict maps and the lack of correlation between physical features of the coffee plantations and elephant visits suggest elephants move along corridors between the eastern and western forests of the district, opportunistically foraging when crossing the plantations. Dung analyses indicate elephants have selectively included ripe coffee berries in their diet. This is, to our knowledge, the first report of wild elephants feeding on coffee berries. If this new behaviour spreads through the population, it will compound an already severe conflict situation. The behavioural plasticity, the multiplicity of stakeholders involved, the difficulty in defining the problem and the limits of technical solutions already proposed suggest that HEC in Kodagu has the ingredients of a "wicked" problem whose resolution will require more shared understanding and problem solving work amongst the stakeholders.

Elephants also like coffee: trends and drivers of human-elephant conflicts in coffee agroforestry landscapes of Kodagu, Western Ghats, India.

Kodagu district produces 2% of the world's coffee, in complex, multistoried agroforestry systems. The forests of the district harbour a large population of the Asian elephant (Elephas maximus). The combined effects of high elephant density and major landscape changes due to the expansion of coffee cultivation are the cause of human-elephant conflicts (HEC). Mitigation strategies, including electric fences and compensation schemes implemented by the Forest Department have met with limited success. Building on previous studies in the area, we assessed current spatial and temporal trends of conflict, analysed local stakeholders' perceptions and identified factors driving elephants into the estates. Our study, initiated in May 2007, shows that the intensity of HEC has increased over the last 10 years, exhibiting new seasonal patterns. Conflict maps and the lack of correlation between physical features of the coffee plantations and elephant visits suggest elephants move along corridors between the eastern and western forests of the district, opportunistically foraging when crossing the plantations. Dung analyses indicate elephants have selectively included ripe coffee berries in their diet. This is, to our knowledge, the first report of wild elephants feeding on coffee berries. If this new behaviour spreads through the population, it will compound an already severe conflict situation. The behavioural plasticity, the multiplicity of stakeholders involved, the difficulty in defining the problem and the limits of technical solutions already proposed suggest that HEC in Kodagu has the ingredients of a "wicked" problem whose resolution will require more shared understanding and problem solving work amongst the stakeholders.

A study to correlate rotenone induced biochemical changes and cerebral damage in brain areas with neuromuscular coordination in rats.

Rotenone induces neurotoxicity but its correlation with biochemical and cerebral changes in rat brain regions are not well defined. In the present study rotenone was administered (3, 6 and12mug/mul) intranigrally in adult male SD rats and its effect was assessed on neuromuscular coordination and in different brain areas viz. striatum (STR), mid-brain (MB), frontal cortex (FC) and hippocampus (HP) cerebral and biochemical changes on 1st and 7th day after treatment. All the doses of rotenone significantly impaired neuromuscular coordination performance on Rota rod test on 1st and 7th day. TTC staining showed significant increase in cerebral injury volume on 1st and 7th day after rotenone treatment indicating mitochondrial enzyme deficiency but increase after 7th day was less that after 1st day. Rotenone treated rats showed significant decrease in GSH and increase in MDA in different brain regions though the pattern was varied. After 1 day of rotenone (6 and 12mug) treatment significant decrease in GSH was observed in STR and MB while MDA was significantly increased only in MB. The maximal effect on GSH and MDA was obtained in STR and MB on 7th day after treatment with 12mug dose of rotenone. Thus, based on the occurrence of changes, it may be suggested that impairment of neuromuscular coordination is inked to oxidative stress rather than mitochondrial enzyme deficiency, all the processes are correlated with each other with the progression of time. MB appeared as most sensitive brain area towards rotenone toxicity.

Population pharmacokinetics of acyclovir in children and young people with malignancy after administration of intravenous acyclovir or oral valacyclovir.

Acyclovir is effective in the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The aim of this study was to characterize the population pharmacokinetics of acyclovir observed following treatment with intravenous acyclovir and oral valacyclovir (valaciclovir) in young people with malignancy. Plasma acyclovir concentration-time data were collected from 43 patients (age range, 9 months to 20 years) who had been given multiple doses of acyclovir (5 mg/kg of body weight) and/or valacyclovir (10 mg/kg). Nonlinear mixed-effect modeling was employed to analyze acyclovir population pharmacokinetics and identify influential covariates. Simulations (n = 1,000) were conducted to explore the ability of the current doses to maintain acyclovir concentrations above the recommended 50% inhibitory concentration for HSV or VZV (0.56 mg/liter or 1.125 mg/liter, respectively) for more than 12 h. A one-compartment pharmacokinetic model with first-order elimination best described the acyclovir concentration-time data. The population mean estimates for clearance (CL), volume of distribution (V), absorption rate (k(a)), and bioavailability (F) were 3.55 liters/h, 7.36 liters, 0.63 h(-1), and 0.60, respectively. Inclusion of body weight and estimated creatinine CL (CL(CR)) in the final model reduced the interindividual variabilities in CL and V from 61% to 24% and from 75% to 36%, respectively. Simulations revealed that with the use of the current doses, maximal efficacy can be achieved in over 45% of patients weighing 25 to 50 kg and with CL(CR) levels of 2.0 to 4.0 liters/h/m(2), but only in a much smaller proportion of patients, with low weights (10 kg) and high CL(CR)s (5.5 liters/h/m(2)), suggesting that higher doses are required for this subgroup. This validated population pharmacokinetic model for acyclovir may be used to develop dosing guidelines for safe and effective antiviral therapy in young people with malignancy.

HPLC-UV assay for monitoring total and unbound mycophenolic acid concentrations in children.

A simple, accurate and sensitive HPLC method was developed for measuring total and unbound mycophenolic acid (MPA) in human plasma. Total MPA was extracted by protein precipitation and ultrafiltration was used to assess unbound MPA concentrations. The supernatant (20 microL) or ultrafiltrate (100 microL) was injected onto a C(18) HPLC column with a mobile phase of 0.05 m sodium phosphate buffer (pH 2.31)-acetonitrile (55:45, v/v for total MPA; 50:50 for unbound MPA) with UV detection at 254 nm. The extraction recovery was over 93% and reproducible. The assay was linear over the concentration range of 0.07-50 mg/L for total MPA and 4-1500 microg/L for unbound MPA. Intra- and inter-day assay reproducibility was less than 10%. Detection limits were 0.04 mg/L and 2 microg/L for total and unbound MPA, respectively. The assay utility was established in samples collected from five paediatric bone marrow transplant recipients who were receiving intravenous doses of mycophenolate mofetil. In these patients MPA concentrations ranged from 0.07 to 7.83 mg/L and unbound drug concentrations ranged from 2.1 to 107.5 microg/L. This method can be effectively applied to MPA pharmacokinetics in paediatric patients.

HPLC-fluorescence assay for acyclovir in children.

A simple, accurate, reliable and sensitive HPLC method was developed and validated for quantitating acyclovir in human plasma. Sample (100 microL) preparation involved addition of guanosine (internal standard) and protein precipitation with 7% perchloric acid and centrifugation. Supernatant (20 microL) was injected onto a C18 HPLC column with a mobile phase of 0.05 m sodium phosphate buffer-acetonitrile (pH 2.35, 992:8, v/v) with 25 microL of 0.4 m tetrabutylammonium hydroxide titrant and fluorescence detection (excitation, 260 nm; emission, 375 nm). Analyte recovery was 101% and the assay response was linear over the acyclovir concentration range of 0.1-20 mg/L. Intra- and inter-day accuracy and precision were less than 7%. The limit of detection and limit of quantitation were 0.033 and 0.1 mg/L, respectively. In five paediatric oncology patients administered intravenous acyclovir, concentrations ranged from 0.24 to 43.65 mg/L. This method can be used to measure acyclovir concentrations in paediatric patients.

Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants.

BACKGROUND: There are no published reference intervals for concentrations of alpha-fetoprotein (AFP) in the cerebrospinal fluid (CSF) of normal infants. The presence of abnormal concentrations of AFP in plasma or CSF may indicate the presence of a teratoma or a germ cell tumour with yolk sac elements. We measured CSF AFP in infants who did not have malignancy in order to determine its reference intervals. METHODS: AFP was measured in the CSF and/or plasma in 128 infants. Of these, 91 infants had CSF AFP measurements, 94 infants had plasma AFP measurements and in 60 infants AFP concentrations were determined in paired CSF and plasma samples. The patients ranged in age from 1 to 110 days. Both CSF and plasma AFP concentrations were measured by a microparticle enzyme immunoassay using an AxSYM analyser. RESULTS: Using ages corrected for prematurity, the median CSF AFP concentration for babies -69 to 31 days old was 61 kIU/L (5th-95th centile: 2-889 kIU/L), while the median CSF AFP concentration for infants 32 to 110 days was 1.2 kIU/L (5th-95th centile: 0.1-12.5 kIU/L). By age 6 weeks, the concentrations were close to those found in adult plasma and all CSF AFP concentrations from infants with a corrected age over 2 months were <3 kIU/L. CONCLUSION: We have defined reference intervals for CSF AFP concentrations in infants. These results may assist in the diagnosis of CNS tumours, particularly congenital CNS tumours containing yolk sac elements.