Does livestock-Manure-Derived Biochar Suitable for the Stabilization of Cadmium and Zinc in Contaminated Soil?

Both livestock-manure and livestock-manure-derived biochar have been used to remediate heavy metal-contaminated soil. However, direct comparisons of the heavy metal stabilization efficiency of livestock-manure and EQC-manure-biochar (derived from an equal quantity of corresponding livestock-manure) are limited. In the present study, the effect of livestock-manures and EQC-manure-biochars on soil properties and heavy metal bioavailability and leachability were compared using two contrasting soils (Ferralsols and Fluvisols). The results showed that both the livestock-manures and EQC-manure-biochars significantly changed soil pH, available phosphorus, available potassium, alkaline nitrogen and organic matter content (p < 0.05), but the trends were variable. In Ferralsols, the DTPA-extractable Cd and Zn decreased by -0.38%~5.70% and - 3.79%~9.98% with livestock-manure application and by -7.99%~7.23% and - 5.67%~7.17% with EQC-manure-biochars application. In Fluvisols, the DTPA-extractable Cd and Zn decreased by 13.39%~17.41% and - 45.26%~14.24% with livestock-manure application and by 10.76%~16.90% and - 36.38%~16.37% with EQC-manure-biochar application. Furthermore, the change in TCLP-extractable Cd and Zn in both soils was similar to that of DTPA-extractable Cd and Zn. Notably, the Cd and Zn stabilization efficiency of the EQC-manure-biochars was no better than that of the corresponding livestock-manures. These results suggest that the use of livestock-manure-derived biochar is not cost-effective for the remediation of heavy metal-contaminated soil.

Bioavailability and Toxicity of nano Copper Oxide to Pakchoi (Brassica Campestris L.) as Compared with bulk Copper Oxide and Ionic Copper.

The increasing use of copper oxide nano particles (nCuO) as nano-fertilizers and pesticides have raised concerns over their impact on soil environment and agricultural products. In this study, two nCuO with different shapes, namely spherical nCuO (CuO NPs) and tubular nCuO (CuO NTs), were selected to investigate their bioavailability and toxicity to pakchoi in two soils with different properties. At the meantime, CuO bulk particles (CuO BPs) and Cu(NO3)2 were used for comparison. Results showed that all the Cu treatments increased the DTPA extractable (DTPA-Cu) concentrations in GD soil (acidic) more than in HN soil (alkaline). The DTPA-Cu concentrations increased in the order of Cu(NO3)2 ≈ CuO NPs > CuO BPs ≈ CuO NTs in GD soil and Cu(NO3)2 > CuO NPs > CuO BPs ≈ CuO NTs in HN soil. While for the contents of Cu in the aerial parts of pakchoi, the order is CuO NPs > Cu(NO3)2 > CuO NTs ≈ CuO BPs in GD soil and CuO NPs ≈ Cu(NO3)2 > CuO BPs ≈ CuO NTs in HN soil. Only CuO NPs reduced pakchoi biomass in GD soil. There are no significant difference among CuO NPs, CuO BPs, and Cu(NO3)2 in reducing the chlorophyll contents in pakchoi in HN soil, whereas in GD soil, CuO NPs and CuO BPs led to significantly lower chlorophyll contents in pakchoi compared to Cu(NO3)2. Additionally, CuO NPs and Cu(NO3)2 increased Mn and Mo in pakchoi leaf in HN soil, while increased Zn in pakchoi leaf in GD soil. These results indicated that CuO NPs showed higher or comparable toxicity and bioavailability to pakchoi compared with Cu(NO3)2 depending on soil properties, and nCuO are more easily to be transferred from roots to the aerial parts than CuO BPs and Cu(NO3)2.

Effect of biological sewage sludge and its derived biochar on accumulation of potentially toxic elements by corn (Zea mays L.).

The land application of sewage sludge can cause different environmental problems due to the high content of potentially toxic elements (PTEs). The objective of this study was to compare the effect of urban biological sewage sludge (i.e. the waste of activated sludge process) and its derived biochar as the soil amendments on the bioavailability of PTEs and their bioaccumulation by corn (Zea mays L.) under two months of greenhouse conditions. The soil was treated by adding biochar samples at 0 (control), 1, 3, 5% w/w. The diethylenetriamine pentaacetic acid (DTPA)-extractable concentrations of PTEs including Zn, Pb, Cd, Cr, Ni, Fe, and Cu in soil and their accumulation by plant shoot and root were measured. Conversion of the biological sewage sludge into the biochar led to decrease the PTEs bioavailability and consequently decreased their contents in plant tissues. The DTPA extractable metal concentrations of produced biochar in comparison to the biological sewage sludge reduced 75% (Cd), 65% (Cr), 79% (Ni and Pb), 76% (Zn), 91% (Cu) and 88% (Fe). Therefore, the content of Ni, Fe, Zn and Cd in corn shoot was decreased 61, 32, 18 and 17% respectively in application of 5% biochar than of raw sewage sludge. Furthermore, the application of 5% biochar enhanced the physiological parameters of the plants including shoot dry weight (twice) and wet weight (2.25 times), stem diameter (1.70 times), chlorophyll content (1.03 times) in comparison to using 5% raw sewage sludge. The results of the study highlight that application of the biochar derived from urban biological sewage sludge in soil could decrease the risk of PTEs to the plant.

Interrogating the Theranostic Capacity of a MUC16-Targeted Antibody for Ovarian Cancer.

Aberrantly expressed glycans on mucins such as mucin-16 (MUC16) are implicated in the biology that promotes ovarian cancer (OC) malignancy. Here, we investigated the theranostic potential of a humanized antibody, huAR9.6, targeting fully glycosylated and hypoglycosylated MUC16 isoforms. Methods: In vitro and in vivo targeting of the diagnostic radiotracer [89Zr]Zr-DFO-huAR9.6 was investigated via binding experiments, immuno-PET imaging, and biodistribution studies on OC mouse models. Ovarian xenografts were used to determine the safety and efficacy of the therapeutic version, [177Lu]Lu-CHX-A″-DTPA-huAR9.6. Results: In vivo uptake of [89Zr]Zr-DFO-huAR9.6 supported in vitro-determined expression levels: high uptake in OVCAR3 and OVCAR4 tumors, low uptake in OVCAR5 tumors, and no uptake in OVCAR8 tumors. Accordingly, [177Lu]Lu-CHX-A″-DTPA-huAR9.6 displayed strong antitumor effects in the OVCAR3 model and improved overall survival in the OVCAR3 and OVCAR5 models in comparison to the saline control. Hematologic toxicity was transient in both models. Conclusion: PET imaging of OC xenografts showed that [89Zr]Zr-DFO-huAR9.6 delineated MUC16 expression levels, which correlated with in vitro results. Additionally, we showed that [177Lu]Lu-CHX-A″-DTPA-huAR9.6 displayed strong antitumor effects in highly MUC16-expressing tumors. These findings demonstrate great potential for 89Zr- and 177Lu-labeled huAR9.6 as theranostic tools for the diagnosis and treatment of OC.

Adsorption removal of cationic dyes from wastewater using the corn straw modified with diethylenetriaminepentacetic acid ligand.

Taking the thiazide cationic dye methylene blue (MB), triphenylmethane cationic dye crystal violet (CV), monoazo cationic dye cationic red 46 (R-46), and polycarboxycyanine cationic dye cationic rosé FG (P-FG) as the research objects, the adsorption behaviors of a self-made corn straw modified adsorbent HQ-DTPA-I for the dyes were investigated in depth. Under optimized conditions, HQ-DTPA-I can quickly adsorb most dyes within 3 min and reach equilibrium adsorption in 15-20 min. The removal rates of HQ-DTPA-I to MB, CV, R-46 and AP-FG can reach 95.28 %, 99.78 %, 99.28 % and 98.53 %, respectively. It also has good anti-interference ability for common ions present in most actual dye wastewater. For six consecutive adsorption-desorption cycles, the adsorption performance of HQ-DTPA-I can still reach 80.17 %, 81.61 %, 90.77 % and 83.48 % of the initial adsorption capacity, indicating good recovery performance. Based on Gaussian density functional theory to calculate its surface potential energy, it is found that the adsorption mechanism of HQ-DTPA-I for the cationic dyes is mainly due to the electrostatic interaction between the carboxyl groups in ligand DTPA and amino groups in dye molecules.

Retroperitoneoscopic Simple Nondismembered Pyeloplasty with Da Vinci Si Assistance to Prevent Alignment Shift.

Aims: Retroperitoneoscopic simple nondismembered pyeloplasty (SNDP) with da Vinci Si assistance was developed because of a possible risk for alignment shift after retroperitoneoscopic diamond-shaped bypass pyeloplasty (Diamond-Bypass; DP). Outcomes of SNDP and DP were compared. Materials and Methods: For SNDP, a small longitudinal incision is made on the border of the dilated pelvis and narrowed ureter at the ureteropelvic junction (UPJ). Extending this incision toward the pelvis allows identification of mucosa while maintaining the integrity of surrounding tissues that are so thin and fragile that they will not influence lumen alignment. Data for DP were obtained from a previously published article. Results: For SNDP (n = 3), mean age at surgery was 2.67 years (range: 1-4), mean operative time was 176 minutes. Mean postoperative Society of Fetal Urology (SFU) grades for hydronephrosis were 1.2, 0.7, and 0.6, 1, 2, and 3 months after stent removal, respectively. Postoperative diethylenetriaminepentaacetic acid (DTPA) was normal (n = 3). For DP (n = 5) mean age at surgery was 4.3 years (range: 1-14), mean operative time was 189 minutes. Mean postoperative SFU grades were 2.8, 2.2, and 1.6, respectively. Postoperative DTPA was normal (n = 4) and delayed (n = 1). All SNDP and DP were asymptomatic by 3 months after stent removal. Conclusion: Both SNDP and DP have favorable outcomes. If the UPJ is located at the lowest end of the renal pelvis, SNDP may improve hydronephrosis more quickly.

Potential of combined reactor and static composting applications for the removal of heavy metals and antibiotic resistance genes from chicken manure.

Chicken manure (CM) can pose a serious threat to environmental and human health, and need to be managed properly. The compost can effectively treat CM. However, there is limited research on the heavy metals and antibiotic resistance genes (ARGs) during compost CM. In this study, the combined application of reactor and static composting (RSC) was used to produce organic fertilizer of CM (OCM), and heavy metals, ARGs and bacterial community structure was investigated. The results show that RSC could be used to produce OCM, and OCM meet the National organic fertilizer standard (NY/T525-2021). Compared to the initial CM, DTPA-Cu, DTPA-Zn, DTPA-Pb, DTPA-Cr, DTPA-Ni and DTPA-As in OCM decreased by 40.83%, 23.73%, 34.27%, 38.62%, 16.26%, and 43.35%, respectively. RSC decreased the relative abundance of ARGs in CM by 84.06%, while the relative abundance of sul1 and ermC increased. In addition, the relative abundance and diversity of ARGs were mainly influenced by the bacterial community, with Actinobacteria, Firmicutes, and Proteobacteria becoming the dominant phyla during composting, and probably being the main carriers and dispersers of most of the ARGs. Network analyses confirmed that Gracilibacillus, Lactobacillus, Nocardiopsis, Mesorhizobium and Salinicoccus were the main potential hosts of ARGs, with the main potential hosts of sul1 and ermC being Mesorhizobium and Salinicoccus. The passivation and physicochemical properties of heavy metals contribute to the removal of ARGs, with sul1 and ermC being affected by the toal heavy metals. Application of RSC allows CM to produce mature, safe organic fertilizer after 32 d and reduces the risk of rebound from ARGs, but the issues of sul1 and ermC gene removal cannot be ignored.

Limestone and yellow gypsum can reduce cadmium accumulation in groundnut (Arachis hypogaea): A study from a three-decade old landfill site.

Cadmium (Cd) toxicity has cropped up as an important menace in the soil-plant system. The use of industrial by-products to immobilise Cd in situ in polluted soils is an interesting remediation strategy. In the current investigation, two immobilizing amendments of Cd viz., Limestone (traditionally used) and Yellow gypsum (industrial by-product) have been used through a green-house pot culture experiment. Soil samples were collected from four locations based on four graded levels of DTPA extractable Cd as Site 1 (0.43 mg kg-1), Site 2 (0.92 mg kg-1), Site 3 (1.77 mg kg-1) and Site 4 (4.48 mg kg-1). The experiment was laid out in a thrice replicated Factorial Complete Randomized Design, with one factor as limestone (0, 250, 500 mg kg-1) and the other being yellow gypsum (0, 250, 500 mg kg-1) on the collected soils and groundnut was grown as a test crop. Results revealed that the DTPA-extractable Cd content in soil and Cd concentration in plants decreased significantly with the increasing doses of amendments irrespective of initial soil available Cd and types of amendment used. The effect of amendment was soil specific and in case of Site 1 (low initial Cd) the effect was more prominent. The reduction in DTPA-extractable Cd in combined application of limestone and yellow gypsum @500 mg kg-1 over the absolute control in soil under groundnut for the sites was by far the highest with the values of 83.72%, 77.17%, 48.59% and 40.63% respectively. With the combined application, Target Cancer Risk (TCR) of Cd was also reduced. Hence, combined application of limestone and yellow gypsum can be beneficial in the long run for mitigating Cd pollution.

Evaluation of 177Lu-Labeled Pertuzumab F(ab')2 Fragments for HER2-Positive Cancer Targeting: A Comparative In Vitro and In Vivo Study.

Background: Radiolabeled antibody fragments present a promising opportunity as theranostic agents, offering distinct advantages over whole antibodies. In this study, the authors investigate the potential of [177Lu]Lu-DTPA-F(ab')2-pertuzumab as a theranostic agent for precise targeting of human epidermal growth factor receptor 2 (HER2)-positive cancers. Additionally, the authors aim to quantitatively assess the binding synergism in the presence of cold trastuzumab. Materials and Methods: F(ab')2-pertuzumab was prepared by pepsin digestion and conjugated with a bifunctional chelator. The immunoconjugate was radiolabeled with 177Lu and characterized by chromatography techniques. Binding parameters (affinity, specificity, and immunoreactivity) and cellular binding enhancement studies were evaluated in HER2-overexpressing and triple-negative cell lines. The in vivo enhancement in tumor uptake of the radiolabeled immunoformulation was assessed in severe combined immunodeficient (SCID) mice bearing tumors, both in the presence and absence of unlabeled trastuzumab. Results: The formulation of [177Lu]Lu-DTPA-F(ab')2-pertuzumab could be prepared in high yields and with consistent radiochemical purity, ensuring reproducibility. Comprehensive in vitro and in vivo evaluation studies confirmed high specificity and immunoreactivity of the formulation toward HER2 receptors. Binding synergism of radiolabeled pertuzumab fragments in the presence of trastuzumab to HER2 receptors was observed. Conclusions: The radioformulation of [177Lu]Lu-DTPA-F(ab')2-pertuzumab holds great promise as a targeted approach for addressing HER2-positive cancers. A potentially effective strategy to amplify therapeutic efficacy involves dual epitope targeting by combining radiolabeled pertuzumab with cold trastuzumab.

Preparation of magnetic DTPA-modified chitosan composite microspheres for enhanced adsorption of Pb(II) from aqueous solution.

In this study, magnetic DTPA-modified chitosan composite microspheres (MDCM) were prepared by reverse emulsion-double crosslinking method (carbodiimide followed by glutaraldehyde) for removal of Pb(II) from aqueous solution. The obtained magnetic adsorbents were characterized by FTIR, SEM, XRD, VSM, BET, and 13C NMR. The effects of the pH, contact time, initial concentration, and competitive metal cations (Na(I), Ca(II), or Mg(II)) on Pb(II) adsorption were investigated. The results revealed that MDCM exhibited high removal performance over a wide pH range and in the presence of competitive metal cations. The maximum adsorption capacity of MDCM for Pb(II) is 214.63 mg g-1 at pH 3, which is higher than most recently reported magnetic adsorbents. Adsorption kinetics and isotherms can be described by the pseudo-second-order model and Langmuir model, respectively. In addition, MDCM is easy to regenerate and can be reused five cycles with high adsorption capacity. Finally, the adsorption mechanism was further revealed by FTIR and XPS analysis. Overall, MDCM has practical application potential in removing Pb(II) from contaminated wastewater due to its high adsorption efficiency, good reusability, and convenient magnetic separation.

Assessing regional hepatic function changes after hypertrophy induction by radioembolisation: comparison of gadoxetic acid-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy.

BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.

Design, development and bio-evaluation of a novel radio-ligand 99mTc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent.

Over-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc was achieved in an excellent yield of 98.0 ± 0.5% using stannous chloride as a reducing agent. The radioligand was found to be stable in human serum up-to 24 h, bio-compatible with less than 4% hemolysis, and exhibited high binding with sigma receptors isolated from rat liver membrane (Kd of 16.32 ± 4.93 nM and Bmax of 0.5232 ± 0.06 pmol/mg). Bio-distribution studies in triple-negative breast tumor bearing nude mice showed high tumor uptake after 30 min of injection with tumor/muscle (T/M) ratio of 3.58 ± 0.09. At 240 min, the T/M ratio (2.84 ± 0.20) decreased by 35% when administered in sigma blocked tumor bearing mice (1.81 ± 0.16) suggesting the selectivity of the ligand. Tumor imaging in gamma camera indicated a contrast of 3.56 at 30 min p.i. The above findings indicate that the ligand 99mTc-THQ-DTPA binds to sigma-2 receptors with high affinity and has potential for triple-negative breast tumor imaging.

Accumulation of livestock manure-derived heavy metals in the Hexi Corridor oasis agricultural alkaline soil and bioavailability to Chinese cabbage (Brassica pekinensis L.) after 4-year continuous application.

Hexi Corridor is one of the most important base of vegetable producing areas in China. Livestock manure (LM) applied to agricultural field could lead to soil heavy metal (HM) pollution. Previous studies have focused on HM pollution following LM application in acidic polluted soils; however, fewer studies have been conducted in alkaline unpolluted soils. A 4-year field vegetable production experiment was conducted using pig manure (PM) and chicken manure (CM) at five application rates (0, 15, 30, 45, and 60 t ha-1) to elucidate potential risks of HMs in an alkaline unpolluted soil in the Hexi Corridor oasis agricultural area and HM uptake by Chinese cabbage. The results showed that LM application caused a significant build-up of Cu, Zn, Pb, Cd, and Ni content in topsoil by 30.6-99.7%, 11.4-51.7%, 1.4-31.3%, 5.6-44.9%, 14%-40.8%, respectively. The Cd, Cu, Zn could potentially exceed the soil threshold in next 8-65 years after 15-60 t ha-1 LM application. Under LM treatment, the soil DTPA-extractable Cu, Zn, Fe, the acid-extractable fraction of Cu, Zn, Fe, Cd, Ni, and the Oxidable fraction of Cu, Zn, Fe, Mn, Cd, Ni significantly increased, but the DTPA-extractable Pb, Cd, the acid-extractable fraction of Pb, and the reducible fraction of Cd significantly decreased. Cu and Zn could migrate to the deeper soil and relatively increase in DTPA-extracted Cu, Zn were found in 20-40 cm soil depth after LM application. The pH and SOM could influence the bioavailability of HMs in soil. The bioaccumulation factor and transfer factor (TF) values were <1 except Mn (TF > 1). HMs in leaf did not approach the threshold for HM toxicity due to the "dilution effect". Recommend the type of manure was the PM and the annual PM application rate was 30 t ha-1 to ensure a 20-year period of clean production in alkaline unpolluted Fluvo-aqiuc vegetable soils.

A comparative study on the quality of in vivo labeled red blood cell radionuclide ventriculography images employing different freeze-dried reagents.

Radionuclide ventriculography or Multi Gated Acquisition (MUGA) employing [ 99m Tc]Technetium red blood cell (RBC) labeling is considered the gold standard for cardiotoxicity assessments in cancer patients undergoing chemotherapy. This in-vivo RBC labeling technique involves the reduction of [ 99m Tc]Technetium by the stannous chloride present in freeze-dried reagent kits, with the pyrophosphate kit (PYP) being the most employed for this purpose. The literature, however, describes diethylenetriaminepentaacetic acid (DTPA) as an alternative to PYP, although a lack of comparative data from MUGA images between both reagents is noted. A retrospective cross-sectional observational study was conducted at the Brazilian National Cancer Institute Nuclear Medicine Service concerning 80 randomized MUGA images, 20 obtained employing DTPA between 2020 and 2023 and 60 obtained employing PYP between 2017 and 2020, applying the mean count per pixel (ct/pixel) and heart background (C/F) ratios as quality image indicators. Although the heart ct/pixel ratio was statistically lower in the DTPA images compared with PYP ( P  = 0.02), the C/F ratio was statistically similar when comparing both radiopharmaceuticals ( P  = 0.697). A semi-quantitative analysis of MUGA images obtained with DTPA and PYP indicates similar image quality, supporting the use of DTPA as an alternative to PYP without compromising diagnostic interpretations.

Addition of bioimpedance-derived body cell mass improves performance of serum creatinine-based GFR estimation in a chronic kidney disease cohort.

PURPOSE: Serum creatinine-based glomerular filtration rate (GFR) estimating equations are imprecise and systemic overestimate GFR in chronic kidney disease (CKD) populations with low muscle mass. Bioimpedance devices can measure body cell mass (BCM), a surrogate for muscle mass which has been included in a published GFR estimating equation. This BCM GFR equation is validated and compared with MDRD and CKD-EPI 2021 equations in an Indian CKD population. METHODS: Patients with stable CKD stages 1-5 and voluntary kidney donors underwent measurement of serum creatinine, DTPA GFR and bioimpedance on the same day. BCM GFR was tested for consistency, agreement and performance with respect to DTPA GFR. RESULTS: A total of 125 study participants were enrolled, including 106 patients with CKD (Stage 1: 8; stage 2: 32, stage 3: 42, stage 4: 20 and stage 5: 4 patients) and 19 voluntary kidney donors, with 66% males, and a mean age of 43.3 (± 16.5) years. The median bias of BCM GFR was 5.45 ml/min/1.73 m2 [95% confidence interval (CI) 4.2-8.3], absolute precision was 10.16 ml/min/1.73 m2 [95% CI 4.5-12.6], P30 was 59.1% [95% CI 50.0-67.7] and accuracy was 8.62% [95% CI 6.4-20.0]. Kappa measurement of agreement was the highest for BCM GFR-based staging (0.628 vs 0.545 for MDRD and 0.487 for CKD-EPI). CONCLUSION: BCM-based GFR estimating equation performed better than MDRD and CKD-EPI equations in this Indian CKD population, and BCM GFR-based KDIGO staging was associated with lesser misclassification than the MDRD and CKD-EPI equations. TRIAL REGISTRATION (PROSPECTIVE): Clinical Trials Registry of India (CTRI/2019/11/021850).

Zinc deficiency induced by the chelating agent DTPA and its regulatory interpretation for developmental toxicity classification.

Aminocarboxylic acid (ethylenediamine-based) chelating agents such as DTPA are widely used in a variety of products and processes. Recently, DTPA was classified in the European Union as a developmental toxicant CLP Category 1B. However, according to the CLP regulation (CLP, 2008) classification as a developmental toxicant requires a chemical to possess an intrinsic, specific property to do so. This paper provides overwhelming evidence that shows the developmental toxicity only seen at a sustained high dose of 1000 mg DTPA/kg bw/day in rats during pregnancy is mediated by zinc depletion which leads to non-specific secondary effects associated with zinc deficiency. Therefore, based on the CLP regulation itself, viz. the lack of a specific, intrinsic property, supported by significant differences in zinc kinetics and physiology between pregnant rats and pregnant women, DTPA should not be classified as a developmental toxicant. Moreover, classification for developmental toxicity resulting from zinc deficiency, and only observed at high doses, would not increase protection of human health; instead, it will only lead to onerous and disproportionate restrictions being placed on the use of this substance.

Enhancing oral bioavailability of Ca-DTPA by self double emulsifying drug delivery system (SDEDDS).

OBJECTIVE: BCS class III drug (highly soluble, poorly permeable) possesses low oral bioavailability. The research work highlights the utility of self-double emulsifying drug delivery system (SDEDDS) which are stable isotropic mixture of w/o primary emulsion and hydrophilic surfactants for improving oral bioavailability of Ca-DTPA (Calcium diethylenetriamine pentaacetate). Upon oral administration, SDEDDS rapidly emulsifies into w/o/w double emulsions in the aqueous gastrointestinal environment, with hydrophilic drugs entrapped inside oil reservoirs. METHODS: SDEDDS formulation was successfully developed using excipients, that is, medium chain triglycerides, oleic acid, phospholipids, Span 80, Tween 80 using double emulsification technique. RESULTS: The optimized formulation F4 (Aq. phase: 11.6%w,w; MCT & oleic acid: 70.9%w/w; Span 80:17.5%w/w; Lecithin:16%w/w and Tween 80 (10%w/w)) appeared bright yellow liquid which upon dilution appeared milky white within 2 min, droplet size (501.7 nm), pdi value (0.044), zeta potential (-52 mV), entrapment efficiency (79.6 ± 1.63), viscosity (72.2 ± 1.8 mpA.s), significant high cumulative in vitro drug permeation (CDP) and 2.17-fold increase in apparent permeability coefficient. Pharmacokinetic studies in rats showed 1.17-fold increases in AUC of F4 and comparatively higher plasma levels (Cmax) compared with pure drug administered orally. The Absolute (OF4, OD) and Relative bioavailability was found to be 14.52%, 12.35%, and 117.47%, respectively. CONCLUSION: The present studies have clearly demonstrated that SDEDDS could readily form w/o/w double emulsions in vivo with enhanced in vitro and in vivo oral bioavailability. Therefore, considerable augmentation in the rate and extent of oral drug absorption ratified the better performance of the SDEDDS in enhancing the bioavailability of Ca-DTPA.

Temperature-induced changes in DTPA-extractable trace elements: Predicting the potential impact of climate change on the availability of soil elements.

The extraction of trace elements from soil with DTPA is a widely used protocol across laboratories. There is a possible "hidden" discrepancy regarding the results obtained from the extractions, i.e., ambient laboratory temperature and soil properties. In this study, the possible influence of these factors on the extractability of the available forms of Cu, Fe, Pb, Mn, Ni, and Zn, measured with DTPA were studied. Α series of extractions was carried out on a soil sample under normal laboratory temperatures, which fluctuated throughout the year, from 15 to 33.9 °C. In other 144 soil samples, the prevailing physico-chemical properties of soil were evaluated (pH, organic C, clay, CaCO3) that affected the percentage of DTPA extractability relative to the pseudo-total determined content. A strong positive correlation of all metals versus increased ambient temperature was found. Cu had an R2 of 0.897, Fe 0.970, Mn 0.957, Ni 0.938, Pb 0.876, and, Zn 0.922, all highly significant. Extracted Mn exhibited a 6.5-fold increase at the highest temperature of 33.9 οC compared to the lowest. Similar increasing trend was observed for Fe, and Ni, and smaller for Cu, Zn, and Pb. Inherent soil properties affected the percentage of extractability relative to the total content: extractability of Cu, Fe, Mn, and Ni was affected negatively by pH, and the extractability of the studied metals with CaCO3 content. Other soil properties (organic C and clay/sand content) also had an effect, not as pronounced as that of pH and CaCO3. This signifies the necessity of employing standard conditions for routine extractions such as DTPA so that data may be comparable. Also these identified discrepancies may have consequences in the extractability and availability of soil micronutrients and toxic elements regarding climate change. This study aspires to play the role of an initial step towards more robust investigations that would suggest ways of correcting temperature and soil characteristics discrepancies across laboratories.

MRI-Based Interstitial Fluid Velocity Analysis for Drug Delivery Efficiency Evaluation in Tumor.

There are many flow behaviors in solid tumors, including intravascular, bloodstream, and interstitial convection. Studies have shown that tumor interstitial fluid (TIF) is an important part of tumor microenvironment regulation and affects drug delivery and metabolism between tumor cells. Magnetic resonance imaging (MRI) is suitable for detecting the flow rates of liquids in tissues. Clinical phase contrast PC-MRI technology has been designed to observe the blood flow in large vessels such as arteries and veins; however, it is not sensitive enough to deal with slow flow velocity. Our previously developed vertical plane echo PC-MRI technology, the Velocity Mapping sequence, improved the signal-to-noise ratio (SNR) for measuring slow interstitial fluid rate. In this study, this sequence was used to determine the TIF flow rate in MDA-MB-231 human breast tumor cells used in BALB/c nude male mice. Two different sizes of contrast agents were intravenously injected, and the relationship between their distribution and the TIF flow rate was studied for the first time. Combining the results of clinical scanning showed that small-molecule DTPA-Gd (diethylenetriaminepentaacetic acid-gadolinium) was distributed immediately around the tumor margin after the injection. This distribution was positively correlated to the high flow rate area of the TIF before administration. In contrast, nanoparticles NaGdF4-PEG (polyethylene glycol) entered the tumor and reached their peak at 3 h. Drug distribution was negatively correlated with the high-flow-rate region of the TIF. Investigation of the TIF velocity can help better understand the fluid behavior in tumors and its role in drug delivery.

Metallic artifacts-free spectral computed tomography angiography based on renal clearable bismuth chelate.

Computed tomography angiography (CTA) is one of the most important diagnosis techniques for various vascular diseases in clinic. However, metallic artifacts caused by metal implants and calcified plaques in more and more patients severely hinder its wide applications. Herein, we propose an improved metallic artifacts-free spectral CTA technique based on renal clearable bismuth chelate (Bi-DTPA dimeglumine) for the first time. Bi-DTPA dimeglumine owns the merits of ultra-simple synthetic process, approximately 100% of yield, large-scale production capability, good biocompatibility, and favorable renal clearable ability. More importantly, Bi-DTPA dimeglumine shows superior contrast-enhanced effect in CTA compared with clinical iohexol at a wide range of X-ray energies especially in higher X-ray energy. In rabbits' model with metallic transplants, Bi-DTPA dimeglumine assisted-spectral CTA can not only effectively mitigate metallic artifacts by reducing beam hardening effect under high X-ray energy, but also enables accurate delineation of vascular structure. Our proposed strategy opens a revolutionary way to solve the bottleneck problem of metallic artifacts in CTA examinations.