Comparative effects of 17% ethylenediaminetetraacetic acid and 9% etidronic acid applied with different irrigant activation techniques on the release of growth factors from dentin: in vitro study.

BACKGROUND: Growth factors embedded in the extracellular matrix of the dentin play an important role in the migration, proliferation, and differentiation of dental pulp stem cells in regenerative endodontics. In regenerative endodontic treatments, the type of irrigation solution used is crucial for the release of growth factors (GFs) from the dentin matrix. This study evaluated the effectiveness of different irrigant activation techniques (IAT) using two different chelating agents, 17% ethylenediaminetetraacetic acid (EDTA) and 9% etidronic acid (HEDP), in terms of their GF release. METHODS: Seventy-two mandibular premolar teeth were prepared to simulate an open apex. The root fragments were irrigated with 20 ml of 1.5% sodium hypochlorite and 20 ml of saline solution. Eight root fragments were randomly separated for the control group, and the remaining 64 fragments were randomly separated into eight groups based on two different chelating agents (17% EDTA and 9% HEDP) and four different IAT ((conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), sonic activation with EDDY, and XP-endo Finisher (XPF)). TGF-ß1, VEGF-A, BMP-7 and IGF-1 release levels were determined using an ELISA, and statistical analysis was performed using the Kolmogorov-Smirnov test, ANOVA, and the Tukey test (p < .05). RESULTS: Compared to the control group, the experimental groups showed significantly higher GF release when using EDTA or HEDP. Among the activation groups, the EDDY group triggered the highest GF release, and the CNI group triggered the lowest. CONCLUSIONS: IAT with EDTA and HEDP can increase GF release, with EDDY being the most effective IAT method. Using chelating agents with IAT may be beneficial in regenerative endodontic treatments.

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).

BACKGROUND: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). METHODS: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. RESULTS: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. CONCLUSIONS: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).

The effects of etidronate on brain calcifications in Fahr's disease or syndrome: rationale and design of the randomised, placebo-controlled, double-blind CALCIFADE trial.

BACKGROUND: Fahr's disease and syndrome are rare disorders leading to calcification of the small arteries in the basal ganglia of the brain, resulting in a wide range of symptoms comprising cognitive decline, movement disorders and neuropsychiatric symptoms. No disease-modifying therapies are available. Studies have shown the potential of treatment of ectopic vascular calcifications with bisphosphonates. This paper describes the rationale and design of the CALCIFADE trial which evaluates the effects of etidronate in patients with Fahr's disease or syndrome. METHODS: The CALCIFADE trial is a randomised, placebo-controlled, double-blind trial which evaluates the effects of etidronate 20 mg/kg during 12 months follow-up in patients aged ≥ 18 years with Fahr's disease or syndrome. Etidronate and placebo will be administered in capsules daily for two weeks on followed by ten weeks off. The study will be conducted at the outpatient clinic of the University Medical Center Utrecht, the Netherlands. The primary endpoint is the change in cognitive functioning after 12 months of treatment. Secondary endpoints are the change in mobility, neuropsychiatric symptoms, volume of brain calcifications, dependence in activities of daily living, and quality of life. RESULTS: Patient recruitment started in April 2023. Results are expected in 2026 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences. CONCLUSIONS: Fahr's disease and syndrome are slowly progressive disorders with a negative impact on a variety of health outcomes. Etidronate might be a new promising treatment for patients with Fahr's disease or syndrome. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05662111. Registered 22 December 2022, https://clinicaltrials.gov/ct2/show/NCT01585402 .

Bromide triggers efficient peroxymonosulfate activation for phosphonate degradation.

Phosphonates have received a widespread attention in wastewater treatment due to their potential threat to the water environment. Advanced oxidation processes (AOPs) are feasible methods to degrade phosphonates, and most of the coexisting substances in water show a negative factor during their oxidation. However, the effect of bromide (Br-) on the degradation of phosphonates in peroxymonosulfate (PMS) activation is still unclear. Herein, using 1-hydroxyethane 1,1-diphosphonic acid (HEDP) as a target phosphonate, Br- could remarkably enhance the degradation of HEDP in PMS activation compared to the PMS alone. Under the condition of pH = 7.0, the optimal degradation efficiency of HEDP is 84.8% in the PMS/Br- process after 30-min reaction, whereas no significant oxidation is obtained in the PMS/I- and PMS/Cl- processes. Multiple experiments (i.e., electron paramagnetic resonance (EPR), radical quenching experiments and chemical probs) confirm that free bromine, SO4•- and HO• paly a minor role in HEDP removal, and bromine radical species make a dominant responsible for HEDP oxidation. Additionally, NO3-, SO42-, Cl-, and HCO3- have a little effect on the degradation of HEDP, but the HEDP removal is greatly inhibited in the presence of humic acid (HA). However, the degradation efficiency of HEDP using PMS/Br- process in river and sewage is a much higher than UV/persulfate (PDS) and UV/H2O2 processes. This study provides a new sight into the effect of Br- on the degradation phosphonates in PMS activation process.

Dislodgement resistance and structural changes of tricalcium silicate-based cements after exposure to different chelating agents.

This study aimed to evaluate the dislodgement resistance and structural changes of different mineral trioxide aggregate cements (MTA) like Pro-Root MTA, Ortho MTA, and Retro MTA after exposure to sodium hypochlorite (NaOCl), NaOCl-Ethylenediaminetetraacetic acid (EDTA), 1-hydroxyethylidene-1, 1-bisphosphonate (Dual Rinse HEDP), and NaOCl-Maleic acid (MA). The root canal spaces of 150 dentine slices were obturated using tricalcium silicate cements and divided into 3 groups (n = 50): Group1: ProRoot MTA, Group2: Retro MTA, and Group3: Ortho MTA. The samples in each group were further subdivided into four experimental (n = 10) and one control groups (n = 10): 2.5% NaOCl-17% EDTA, Dual Rinse HEDP, 2.5% NaOCl-7% Maleic acid, 2.5% NaOCl, distilled water (control). The dislodgement resistance and structural changes of cements were measured. Use of DR HEDP resulted in higher dislodgement resistance compared to17% EDTA and 7% MA in the samples obturated with Ortho MTA and Pro-Root MTA (p<0.001). In Retro MTA group, samples treated with DR HEDP and 17% EDTA had higher dislodgment resistance compared to 7% MA (p<0.001). On microstructural and elemental analysis of all the three MTA cements, samples treated with 17% EDTA and 7% MA were more amorphous and granular when compared to DR HEDP, which was pettle shaped. Calcium level was decreased more in samples treated with 17% EDTA and 7% MA when compared to DR HEDP.

Safety and effectiveness of risedronate in Paget's disease of bone: postmarketing surveillance study in Japan.

INTRODUCTION: We conducted an all-case postmarketing surveillance study between 2008 and 2017 to evaluate the safety and effectiveness of risedronate for Paget's disease of bone (PDB) in Japan. MATERIAL AND METHODS: This study registered all patients who received once-daily risedronate 17.5 mg for the treatment of PDB and collected data over a 48-week follow-up period per treatment cycle for each patient. RESULTS: The safety analysis set included 184 patients (mean age, 63.7 years), 81 (44.0%) of whom previously received a bisphosphonate. Of them, 41 (22.3%) experienced 72 adverse drug reactions (ADRs), and 8 (4.3%) experienced 14 serious ADRs. Common ADRs included gastrointestinal disorders (20 patients, 10.9%) and hypocalcemia (6 patients, 3.3%). The effectiveness analysis set included 182 patients, 124 of whom completed only one treatment cycle and 58 of whom completed multiple treatment cycles. The proportions of patients who normalized serum alkaline phosphatase (ALP) concentration were 71.1% (113/159 patients) and 67.3% (33/49 patients) for the first and second treatment cycles, respectively. The relapse rate according to ALP levels after the end of treatment for the first cycle was 5.0% (95% confidence interval [CI] = 2.1-11.5) at 24 weeks and 12.9% (95% CI = 7.5-21.7) at 40 weeks. Regarding pain relief, the achievement rates were 70.0% (49/70 patients) and 30.8% (4/13 patients) for the first and second treatment cycles, respectively. CONCLUSION: To conclude, risedronate 17.5 mg/day is safe and effective for treating patients with PDB in daily practice.

Disinfection Efficacy of Electrohydraulic Discharge Plasma against Xanthomonas campestris pv campestris: A Sustainable Seed Treatment Approach.

The prevalence of plant diseases caused by pathogens such as Xanthomonas campestris pv campestris (Xcc) poses a significant challenge to sustainable agriculture, necessitating the development of effective and eco-friendly disinfection methods. In this study, we investigated the efficacy of electrohydraulic discharge plasma (EHDP) as a promising alternative for disinfection against Xcc, a pathogen responsible for black rot in cruciferous vegetables. Unlike conventional gas-phase plasma, EHDP introduces two pivotal components: gas-liquid interface plasma (GLIP) and its consequential byproduct, plasma-activated water (PAW). While GLIP enables dual-phase production of reactive oxygen and nitrogen species (RONS), PAW is a reservoir of liquid-phase long-lived RONS, thereby enhancing its bactericidal efficacy. In our evaluations, we tested EHDP-induced GLIP and EHDP-induced PAW against Xcc cells in both in vitro (Xcc suspension) and in vivo (Xcc-inoculated cabbage seeds) settings, achieving noteworthy results. Within 15 min, these methods eliminated ∼98% of the Xcc cells in suspension. For in vivo assessments, nontreated seeds exhibited an infection rate of 98%. In contrast, both EHDP treatments showed a significant reduction, with ∼60% fewer seeds infected while maintaining ∼90% germination rate. In addition, the liquid-phase RONS in EHDP-PAW may enhance seed vigor with a faster germination rate within the initial 5 days. Remarkably, around 90% of EHDP-PAW-treated seeds yielded healthy seedlings, indicating dual benefits in bacterial suppression and seed growth stimulation. In contrast, the percentage of healthy seedlings from nontreated, Xcc-inoculated seeds was approximately 70%. Our research demonstrates the feasibility of using eco-friendly EHDP in the seed disinfection process.

An electrochlorination process integrating enhanced oxidation of phosphonate to orthophosphate and elimination: Verification of matrix chloridion-induced oxidation mechanism.

Phosphonate used as scale inhibitor is a non-negligible eutrophic contaminant in corresponding polluted waters. Besides, its conversion to orthophosphate (ortho-P) is a precondition for realizing bioavailable phosphorus recovery. Due to the feeble degradation efficiency with less than 30 % from classical Fenton commonly used in industrial wastewater treatment and itself vulnerable to strong inhibition interference of matrix chloride ions, we proposed an electrochemical approach to transform the native salt in the solution into oxidizing substances, sort of achieving beneficial utilization of matrix waste, and enhanced the ortho-P conversion rate of 1-Hydroxyethane-1,1-diphosphonic acid (HEDP) to 89.2 % (± 3.6 %). In electrochlorination system, it was found that HEDP rapidly complexed with Fe(II) and then coordinated in-situ Fe(III) to release free HEDP via intramolecular metal-ligand electron transfer reaction. The subsequent degradation mainly rooted in the oxidation of pivotal reactive species HClO, FeIVO2+ and 1O2, causing C-P and CC bonds to fracture in sequence. Eventually the organically bound phosphorus of HEDP was recovered as ortho-P. This study acquainted the audiences with the rare mechanism of chloridion-triggered HEDP degradation under electrochemical way, as well as offered a feasible technology for synchronous transformation of organically bound phosphorus to ortho-P and elimination from phosphonates.

In Vitro Evaluation of Smear Layer and Debris Removal and Antimicrobial Activity of Different Irrigating Solutions.

OBJECTIVE: The aim of this in vitro study was to compare the smear layer and debris removal and antimicrobial activity of two dual-action irrigating solutions for continuous chelation (Triton; Brasseler, Savannah, USA and Dual Rinse HEDP; Medcem GmbH, Weinfelden, Switzerland) with a dual step irrigation protocol with sodium hypochlorite (NaOCl) followed by ethylenediaminetetraacetic acid (EDTA). METHODS: Thirty single-rooted single-canal teeth were divided into three groups (n=10) and irrigated with Triton, Dual Rinse HEDP mixed with 6% NaOCl and 6% NaOCl/17% EDTA. The teeth were observed under a scanning electron microscope (SEM) to assess the canal wall cleanliness. In addition, 80 dentine discs were contaminated with Candida albicans and 80 discs with Enterococcus faecalis and irrigated with Triton, Dual Rinse HEDP mixed with 6% NaOCl and 6% NaOCl/17% EDTA or not treated (n=20). Fifteen discs were used to evaluate colony-forming units, while 5 discs were analysed by SEM. Data were analysed using the Shapiro- Wilk, Kruskal-Wallis and One-Way ANOVA tests. RESULTS: Triton was statistically more effective than Dual Rinse HEDP and NaOCl/EDTA in removing debris (p<0.05), except with NaOCl/EDTA in the coronal third. Triton was more effective than Dual Rinse HEDP in removing the smear layer from the apical and middle thirds (p<0.05). All the irrigation protocols significantly re- duced the number of E. faecalis. The Triton group showed the lowest number of remaining C. albicans (p<0.05). CONCLUSION: Triton was the most effective irrigation solution in removing debris and as effective as NaOCl/ EDTA in removing the smear layer. Triton showed the highest efficacy against C. albicans. New irrigating solutions that provide continuous chelation may provide an alternative to current irrigation protocols.

Structural Diversity in Antiosteolytic Bisphosphonates: Deciphering Structure-Activity Trends in Ultra Long Controlled Release Phenomena.

Bisphosphonate (BP)-based treatments have been extensively prescribed for bone-related conditions, particularly for osteoporosis. Their low bioavailability creates the need for prescribed dosage increase to reach therapeutic levels but generates a plethora of undesirable side effects. A viable approach to alleviating these issues is to design and exploit controlled release strategies. Herein, the controlled release profiles of 15 structurally characterized BPs (actual drugs and structural analogs) were thoroughly studied from tablets containing three (cellulose, lactose, and silica) or two (cellulose, and silica) excipients in human stomach-simulated pH conditions. The BPs were of two types, alkyl-BPs and amino-BPs. Alkyl-BPs included four derivatives of etidronate (acid, disodium, tetra-sodium, and monopotassium forms), medronic acid, and three analogs of etidronate, in which the -CH3 group was replaced by the moieties -H, -CH2CH2CH3, and -CH2CH2CH2CH2CH3. Amino-BPs included the commercial drugs pamidronate, alendronate, neridronate, and ibandronate, as well as three analog compounds. Release curves were constructed based on data taken from 1H NMR peak integration and were expressed as "% BP release" vs time. The controlled release profiles (initial release rate, plateau value, etc.) were correlated with certain structural features (number of hydrogen and metal-oxygen bonds), showing that the molecular and crystal lattice features of each BP profoundly influence its release characteristics. It was concluded that for all BPs, in general, the initial rate became lower as the total number of lattice interactions increased. For the alkyl-BPs elongation of the alkyl side chain seems to decelerate the release. Amino-BPs, in general, show slower release than the alkyl-BPs. No adverse effects of alkyl- and amino-BP drugs on NIH3T3 cell viability were noted.

Complexation-based selectivity of organic phosphonates adsorption from high-salinity water by neodymium-doped nanocomposite.

Organic phosphonates have been widely used in various industries and are ubiquitous in wastewaters, and efficient removal of phosphonates is still a challenge for the conventional processes because of the severe interferences from the complex water constitutions. Herein, an Nd-based nanocomposite (HNdO@PsAX) was fabricated by immobilizing hydrated neodymium oxide (HNdO) nanoparticles inside a polystyrene anion exchanger (PsAX) to remove phosphonates from high-salinity aqueous media. Batch experiments demonstrated that HNdO@PsAX had an excellent adsorption capacity (∼90.5 mg P/g-Nd) towards a typical phosphonate (1-hydrox-yethylidene-1,1-diphosphonic acid, HEDP) from the background of 8 g/L NaCl, whereas negligible HEDP adsorption was achieved by PsAX. Attractively, various coexisting substances (humic acid, phosphate, citrate, EDTA, metal ligands, and anions) exerted negligible effects on the HEDP adsorption by HNdO@PsAX under high salinity. FT-IR and XPS analyses revealed that the inner-sphere complexation between HEDP and the immobilized HNdO nanoparticles is responsible for HEDP adsorption. Fixed-bed experiments further verified that HNdO@PsAX was capable of successively treating more than 4500 bed volumes (BV) of a synthetic high-salinity wastewater (1.0 mg P/L of HEDP), whereas only ∼2 BV of effective treatment capacity was received by PsAX. The exhausted HNdO@PsAX was amenable to a complete regeneration by a binary NaOHNaCl solution without significant loss in capacity. The capability in removing other organic phosphonates and treating a real electroplating wastewater by HNdO@PsAX was further validated. Generally, HNdO@PsAX exhibited a great potential in efficiently removing phosphonates from high-salinity wastewater.

Novel Treatments for PXE: Targeting the Systemic and Local Drivers of Ectopic Calcification.

Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, ABCC6, encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 4 weeks of age, before the development of ectopic calcification, were treated with ETD, Mino, or both for 18 weeks. Micro-computed tomography, histopathologic examination, and quantification of the calcium content in Abcc6-/- mice treated with both ETD and Mino revealed further reduced calcification than either treatment alone. The effects were associated with reduced serum alkaline phosphatase activity without changes in plasma PPi concentrations. These results suggest that ETD and Mino combination therapy might provide an effective therapeutic approach for PXE, a currently intractable disease.

Cost-effectiveness of weekly gastro-resistant risedronate 35 mg, compared with weekly alendronate 70 mg tablets, in the treatment of postmenopausal osteoporosis in Spain.

Aim: To estimate the cost-effectiveness of treating postmenopausal osteoporosis (PMO) with weekly gastro-resistant risedronate 35 mg gastro-resistant tablets (RIS-GR), compared with weekly alendronate 70 mg tablets (ALN) in Spain. Methods: A probabilistic analysis (second-order Monte Carlo simulation) was performed with a time horizon of 5 years, from the perspective of the Spanish National Health System. The bone fracture probabilities were obtained from a cohort study of 3614 women from USA with PMO treated with RIS-GR (1807) or ALN (1807) (Thomasius, 2022). The pharmacological cost and the cost of fractures were obtained from Spanish sources (€ 2022). The utilities of patients with and without fracture (quality-adjusted life years [QALYs]) were obtained from the medical literature. Results: Compared with ALN, treatment with RIS-GR can avoid 79 fractures (between 75 and 82) every 1000 patients treated, and 0.0119 QALYs would be gained (between 0.0098 and 0.0140) per patient. Additionally, GR-RIS would generate a cost saving per patient of €1994 (€1437-2904) with a probability of 99.7%. The scenario analyses confirmed the stability of the base case results. Conclusion: According to this study, RIS-GR would be the dominant treatment (lower costs with QALY gain) compared with ALN.

Peracetic acid application as an antimicrobial and its residual (HEDP): a holistic approach on the technological characteristics of chicken meat.

The most significant occurrence of food-borne diseases is due to Campylobacter and Salmonella contamination from chicken meat, and for this reason, strict regulations about strategies to improve the control of food pathogens are imposed by food safety authorities. Despite the efforts of poultry industry since the beginning of risk analysis and critical control point to reduce the burden of food-borne illness, technological barriers along the way are increasingly necessary to ensure safe food. The aim of this review was to carry out a scientific approach to the influence of peracetic acid (PAA) as an antimicrobial and its toxicological safety, in particular the stabilizer used in the formulation of PAA, 1-hydroxyethylidene 1,1-diphosphonic acid (HEDP), suggesting the possibility of researching the residual HEDP in meat, which would allow the approval of the PAA by the health authorities of several countries that still restrict it. This review also aims to ascertain the effectiveness of PAA, in different cuts and carcasses, by different application methods, comparing the effectiveness of this antimicrobial with other antimicrobials, and its exclusive or combined use, for the decontamination of poultry carcasses and raw parts. The literature results support the popularity of PAA as an effective intervention against pathogenic bacteria during poultry processing.

Phycoremediation potential and agar yield of red macroalgae (Gracilaria corticata) against HEDP (hydroxyethylidene diphosphonic acid) and CAPB (cocoamidopropyl betaine) detergents and the heavy metal pollutants.

The discharge of raw industrial, agricultural, and domestic wastes leads to an increase in heavy metal (HM) burden and detergents in aquatic environs, which can have destructive effects on aquatic organisms. Agarophyte Gracilaria corticata, a major component of seaweed flora of the southern coast of Iran (Bushehr) that contains agar and red pigments, is one of the economically valuable red marine algae. Agar is one of the important polysaccharides with high economic value, widely used in pharmaceutical, medicinal, and cosmetic product manufacturing industries. The aim of this work was to investigate the effect of 5 HMs and two common surfactants in household and industrial detergents on the agar yield, appearance color, and the red algae's phycoremediation potential against HMs. The metal ions were Zn(II), Cu(II), Ni(II), Mn(II), and Cr(VI), and the surfactants were HEDP and CAPB. The analysis results of samples cultured for 60 days in seawater and polluted environments showed that G. corticata can accumulate copper and nickel. In the presence of detergents without HMs, the amount of extracted agar significantly increased compared to the control sample with no change in algae color. But with increasing concentration of HMs, the amount of agar in seaweed samples decreased significantly, and the algae discolored from red to dark green or yellowish-green color (signs of death in the algae). These results show that increasing of HM pollution and detergents can lead to toxicological effects and reduce the species diversity of red seaweeds in the future.

EGTA-Derived Carbon Dots with Bone-Targeting Ability: Target-Oriented Synthesis and Calcium Affinity.

The bone-targeting mechanism of clinic bisphosphonate-type drugs, such as alendronate, risedronate, and ibandronate, relies on chelated calcium ions on the surface of the bone mineralized matrix for the treatment of osteoporosis. EGTA with aminocarboxyl chelating ligands can specifically chelate calcium ions. Inspired by the bone-targeting mechanism of bisphosphonates, we hypothesize that EGTA-derived carbon dots (EGTA-CDs) hold bone-targeting ability. For the target-oriented synthesis of EGTA-CDs and to endow CDs with bone targeting, we designed calcium ion chelating agents as precursors, including aminocarboxyl chelating agents (EGTA and EDTA) and bisphosphonate agents (ALN and HEDP) for the target-oriented synthesis of aminocarboxyl-derived CDs (EGTA-CDs and EDTA-CDs) and bisphosphonate-derived CDs (ALN-CDs and HEDP-CDs) with high synthetic yield. The synthetic yield of EGTA-CDs reached 87.6%. Aminocarboxyl-derived CDs and bisphosphonate-derived CDs retain the chelation ability of calcium ions and can specifically bind calcium ions. The chemical environment bone-targeting value coordination constant K and chelation sites of EGTA-CDs were 6.48 × 104 M-1 and 4.12, respectively. A novel method was established to demonstrate the bone-targeting capability of chelate-functionalized carbon dots using fluorescence quenching in a simulated bone trauma microenvironment. EGTA-CDs exhibit superior bone-targeting ability compared with other aminocarboxyl-derived CDs and bisphosphonate-derived CDs. EGTA-CDs display exceptional specificity toward calcium ions and better bone affinity than ALN-CDs, suggesting their potential as novel bone-targeting drugs. EGTA-CDs with strong calcium ion chelating ability have calcium ion affinity in simulated body fluid and bone-targeting ability in a simulated bone trauma microenvironment. These findings offer new avenues for the development of advanced bone-targeting strategies.

The use of sodium hypochlorite mixed with etidronic acid during canal preparation increases debris extrusion.

The purpose of this study was to compare the impact of different irrigation protocols on debris extrusion. Single-rooted teeth were distributed into groups based on the irrigation protocols (n = 40): 2.5% NaOCl (biomechanical preparation: 20 mL and final irrigation: 5 mL); 2.5% NaOCl (biomechanical preparation: 20 mL) + 17% EDTA (final irrigation: 2 mL) + 2.5% NaOCl (final irrigation: 3 mL); and a mixture of 5% NaOCl +18% HEDP (biomechanical preparation: 20 mL and final irrigation: 5 mL). The canals were prepared using a reciprocating instrument size 40/0.06. For final irrigation, the groups were reassigned based on the agitation methods (n = 10): (a) no agitation; (b) ultrasonic; (c) sonic; and (d) continuous rotation. The control group (n = 10) received saline solution without agitation. The amount of debris extruded was measured by weight and analysed using One-way ANOVA (α < 0.05). The subgroups treated with NaOCl + HEDP mixture showed a significantly higher amount of extruded debris (p < 0.05), while there was no difference among agitation methods in all groups (p > 0.05).

La-Ca/Fe-LDH-coupled electrochemical enhancement of organophosphorus removal in water: Organophosphorus oxidation improves removal efficiency.

Metal ions or metal (hydrogen) oxides are widely used as active sites in the construction of phosphate-adsorbing materials in water, but the removal of soluble organophosphorus from water remains technically difficult. Herein, synchronous organophosphorus oxidation and adsorption removal were achieved using electrochemically coupled metal-hydroxide nanomaterials. La-Ca/Fe-layered double hydroxide (LDH) composites prepared using the impregnation method removed both phytic acid (inositol hexaphosphate, IHP) and hydroxy ethylidene diphosphonic acid (HEDP) acid under an applied electric field. The solution properties and electrical parameters were optimized under the following conditions: organophosphorus solution pH = 7.0, organophosphorus concentration = 100 mg L-1, material dosage = 0.1 g, voltage = 15 V, and plate spacing = 0.3 cm. The electrochemically coupled LDH accelerates the removal of organophosphorus. The IHP and HEDP removal rates were 74.9% and 47%, respectively in only 20 min, 50% and 30% higher, respectively, than that of La-Ca/Fe-LDH alone. The removal rate in actual wastewater reached 98% in only 5 min. Meanwhile, the good magnetic properties of electrochemically coupled LDH allow easy separation. The LDH adsorbent was characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analysis. It exhibits a stable structure under electric field conditions, and its adsorption mechanism mainly includes ion exchange, electrostatic attraction, and ligand exchange. This new approach for enhancing the adsorption capacity of LDH has broad application prospects in organophosphorus removal from water.