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1.
Combined dimercaptosuccinic acid and zinc treatment in neurological Wilson's disease patients with penicillamine-induced allergy or early neurological deterioration.
Zhu, XQ, Li, LY, Yang, WM, Wang, Y
Bioscience reports. 2020;(8)
Abstract
The clinical data of safety and efficacy of a combined treatment with dimercaptosuccinic acid (DMSA) and Zinc with 2 years' follow-up in 60 neurological Wilson's disease (WD) patients was retrospectively analyzed. All the patients included in the present study were newly diagnosed and initialized with D-penicillamine (DPA) treatment but were found to have either neurological deterioration or allergy, and their treatment was switched to a combined treatment of DMSA and Zinc. Fifty-one patients (85%) had the neurological symptoms improved 1 and 2 years after treatment, 7 (11.67%) experienced a stable neurological condition, and 2 (3.33%) suffered deterioration of neurological symptoms. No early neurological deterioration was observed in all patients. Twenty-five percent patients experienced mild adverse reactions which did not require a discontinuation of the DMSA and Zinc treatment. Our study confirmed the safety and efficacy of the combined DMSA and Zinc therapy as an initial and probably long-term treatment in neurological WD patients.
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2.
Tolerance and effect of sodium thiosulfate in calcific tendinitis of the rotator cuff.
Darrieurtort-Laffite, C, Bertrand-Vasseur, A, Garraud, T, Planche, L, Le Goff, B
Clinical rheumatology. 2020;(2):561-569
Abstract
BACKGROUND Calcific tendinitis of the rotator cuff is one of the most common causes of shoulder pain. Ultrasound-guided percutaneous lavage of calcific tendinopathy is performed when conservative treatments have failed. Sodium thiosulfate (STS) has recently been used with success in the treatment of tumoral calcinosis. The goal of this phase II study was to assess the tolerance and the feasibility of STS lavage of calcific tendinopathy. METHODS We included patient with type hard calcifications. Patients were treated with puncture and lavage followed by injection of STS in the calcification. VAS pain at rest and during activities, ultrasound, and X-ray were evaluated at 1 week and 1 and 3 months. RESULTS Seventeen patients were included. Baseline VAS at rest and during daily activities was a mean 40.2 ± 25.9 and 65.5 ± 21.6 respectively. All patients underwent the entire procedure with no adverse event. Calcium backflow could be obtained in 15 patients (88.2%). Five patients (30%) had more than 50% decrease of their calcific deposit size at 1 month and 8 (47%) patients at 3 months. VAS pain during activities and at rest decreased significantly at 3 months (p = 0.0004; p = 0.001). Efficacy would be demonstrated if 60% of the patients had more than 50% decrease size of their calcification CONCLUSION Overall, STS was well tolerated with no side effect occurring during the procedure and the follow-up. However, no significant effect on calcium disappearance could be demonstrated compared with what is expected without STS. New studies using larger volume and repeated injections of STS are now needed. CLINICAL TRIAL REGISTRATION NUMBER NCT02538939Key Points• Lavage of calcific tendinopathy of the rotator cuff with sodium thiosulfate is feasible• No adverse events have been observed after or in the 3 months after the procedure• We could not demonstrate that sodium thiosulfate increases the chance of calcium disappearance• New studies using larger volume and repeated injections of STS are needed to further explore the interest of sodium thiosulfate in the treatment of calcific tendinopathy.
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Corrosive attacks in the UK - Psychosocial perspectives and decontamination strategies.
Lewis, CJ, Hodgkinson, EL, Allison, KP
Burns : journal of the International Society for Burn Injuries. 2020;(1):213-218
Abstract
Acid attacks, or vitriolage, are defined as violent assaults involving the deliberate throwing of an acid or similarly corrosive substance with the intention to "maim, disfigure, torture or kill" [1]. The Acid Survivors Trust International suggest a prevalence of 1500 attacks reported worldwide per annum, although this is likely to be an underestimate by 40% [2]. The UK is thought to have one of the highest of rates of recorded corrosive attacks, with an increase from 228 attacks in 2012 to 601 in 2016. Most were reported by the London Metropolitan police force followed by Northumbria, Cambridgeshire, Hertfordshire, Greater Manchester and Humberside [[2]]. The chemical agents involved include acids, alkalis, oxidising and reducing agents, alkylating and chelating agents and solvents. They cause injury by producing a chemical interaction which can lead to extensive tissue destruction and extreme pain. Herein, we present a review on the changing epidemiology of corrosive attacks in the UK and currently employed management strategies.
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4.
Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug-Bug Interaction?
Dai, L, Meijers, BK, Bammens, B, de Loor, H, Schurgers, LJ, Qureshi, AR, Stenvinkel, P, Evenepoel, P
Toxins. 2020;(6)
Abstract
Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbial metabolism. Important representatives of gut-derived uremic toxins, including indoxyl sulfate (IndS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAG) and non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP; a marker of vitamin K status), were analyzed in blood samples from 423 patients (65% males, median age 54 years) with ESKD. Demographics and laboratory data were extracted from electronic files. Sevelamer users (n = 172, 41%) were characterized by higher phosphate, IndS, TMAO, PAG and dp-ucMGP levels compared to non-users. Sevelamer was significantly associated with increased IndS, PAG and dp-ucMGP levels, independent of age, sex, calcium-containing phosphate binder, cohort, phosphate, creatinine and dialysis vintage. High dp-ucMGP levels, reflecting vitamin K deficiency, were independently and positively associated with PAG and TMAO levels. Sevelamer therapy associates with an unfavorable gut microbial metabolism pattern. Although the observational design precludes causal inference, present findings implicate a disturbed microbial metabolism and vitamin K deficiency as potential trade-offs of sevelamer therapy.
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5.
The Effects of Long-Term Magnesium Creatine Chelate Supplementation on Repeated Sprint Ability (RAST) in Elite Soccer Players.
Zajac, A, Golas, A, Chycki, J, Halz, M, Michalczyk, MM
Nutrients. 2020;(10)
Abstract
AIM: The aim of the study was to evaluate the effects of 16 weeks of a low dose of magnesium creatine chelate supplementation on repeated sprint ability test (RAST) results in elite soccer players. MATERIALS Twenty well-trained soccer players participated in the study. The players were divided randomly into two groups: the supplemented group (SG = 10) and placebo group (PG = 10). Out of the 20 subjects selected for the study, 16 (SG = 8, PG = 8) completed the entire experiment. The SG ingested a single dose of 5500 mg of magnesium creatine chelate (MgCr-C), in 4 capsules per day, which was 0.07 g/kg/d. The PG received an identical 4 capsules containing corn starch. Before and after the study, the RAST was performed. In the RAST, total time (TT), first and sixth 35 m sprint length (s), average power (AP) and max power (MP) were measured. Additionally, before and after the test, lactate LA (mmol/L) and acid-base equilibrium pH (-log(H+)), bicarbonates HCO3- (mmol/L) were evaluated. Also, in serum at rest, creatinine (mg/dL) concentration was measured. RESULTS After the study, significantly better results in TT, AP and MP were observed in the SG. No significant changes in the RAST results were observed in the PG. After the study, significant changes in the first 35 m sprint, as well as the sixth 35 m sprint results were registered in the SG, while insignificant changes occurred in the PG. A significantly higher creatinine concentration was observed. Also, a higher post-RAST concentration of LA, HCO3- and lower values of pH were observed in April, May and June compared with baseline values. CONCLUSIONS The long timeframe, i.e., 16 weeks, of the low dose of magnesium creatine chelate supplementation improved the RAST results in the SG. Despite the long period of MgCr-C supplementation, in the end of the study, the creatinine level in the SG reached higher but still reference values.
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6.
A study of susceptibility-weighted imaging in patients with Wilson disease during the treatment of metal chelator.
Zhou, X, Xiao, X, Li, XH, Qin, HL, Pu, XY, Chen, DB, Wu, C, Feng, L, Liang, XL
Journal of neurology. 2020;(6):1643-1650
Abstract
OBJECTIVE A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal chelator was done. METHODS 100 untreated WD patients (80 cases of cerebral type, 20 cases of hepatic type, age 20.13 ± 9.12 years old) and 20 normal controls were selected. Neurological symptoms were scored using the modified Young scale. Liver function tests and copper indices were collected. All study objects received SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. Cerebral-type WD patients were treated with D-penicillamine (DPA) (group 1) or Dimercaptopropane Sulfonate (DMPS) + Dimercaptosuccinic Acid (DMSA) (group 2). Hepatic-type WD patients were treated with DPA (group 3). All patients received annual neurological symptom score, liver function, copper indices, and SWI examination. RESULTS At the first year of treatment, score of the modified Young scale in group 2 was lower than that in group 1 (P = 0.023) and lower than that before treatment (P = 0.040). After 2 years of treatment, the score of the modified Young scale in group 1 was lower than that before treatment (P = 0.012). At the second year after treatment, the urinary copper in group 2 was higher than that in group 1 (P = 0.014). Urinary copper was maintained at 200 µg/day in group 1 and 300 µg/day in group 2 after 3 years of treatment. At the first year of treatment, serum copper in group 1 was lower than that in group 2 (P = 0.032). At the first year of treatment, CP values of the pallidum and substantia nigra in group 2 were higher than those in group 1 (P = 0.026, 0.040). At the second year of treatment, CP value of substantia nigra in group 2 was higher than that in group 1 (P = 0.037). After 3 years of treatment, there was no difference in CP values between WD patients and normal controls. CONCLUSIONS Therapy with DMPS and DMSA improves neurological symptoms of WD patients more quickly and leads to less aggravation, compared with therapy with DPA. The metal content in the brain of WD patients was at a low level after 3 years of treatment. DMPS and DMSA can remove metal from brain tissue faster than DPA.
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7.
Phosphate Binders and Nonphosphate Effects in the Gastrointestinal Tract.
Biruete, A, Hill Gallant, KM, Lindemann, SR, Wiese, GN, Chen, NX, Moe, SM
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(1):4-10
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Abstract
Phosphate binders are commonly prescribed in patients with end-stage kidney disease to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for nonphosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end products. Other binders (calcium- and noncalcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota, as some of the iron or organic ligands may be used by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the nonphosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome.
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Transition metal chelators, pro-chelators, and ionophores as small molecule cancer chemotherapeutic agents.
Steinbrueck, A, Sedgwick, AC, Brewster, JT, Yan, KC, Shang, Y, Knoll, DM, Vargas-Zúñiga, GI, He, XP, Tian, H, Sessler, JL
Chemical Society reviews. 2020;(12):3726-3747
Abstract
Cancer is among the leading causes of death worldwide. Although a number of new treatment options have been developed in recent years, there remains a need for improved chemotherapies. The primary challenges facing new cancer drugs include: (1) improving patient quality of life, (2) overcoming drug resistance and (3) lowering reoccurrence rates. Major drawbacks of current chemotherapeutics arise from poor selectivity towards cancer cells, dose limiting toxicities, compliance-reducing side effects, and an inability to address resistance mechanisms. Chemotherapeutics that fail to achieve complete eradication of the disease can also lead to relapse and promote treatment resistance. New strategies to overcome these drawbacks include the use of transition metal chelators and ionophores to alter selectively the concentrations of iron, copper, and zinc in cancer cells. A number of metal chelators have successfully demonstrated cytotoxicity and targeted activity against drug-resistant cancer cells; several have proved effective against cancer stem cells, a significant cause of tumour reoccurrence. However, problems with formulation and targeting have been noted. Recent efforts have thus focused on the design of pro-chelators, inactive versions of chelators that are designed to be activated in the tumour. This is an appealing strategy that may potentially increase efficacy towards cancer-resistant malignant cells. This Tutorial Review summarizes recent progress involving transition metal chelators, pro-chelators, and ionophores as potential cancer chemotherapeutics. We will focus on the reported agents that are able to coordinate iron, copper, and zinc.
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Benefits and Detriments of Gadolinium from Medical Advances to Health and Ecological Risks.
Unruh, C, Van Bavel, N, Anikovskiy, M, Prenner, EJ
Molecules (Basel, Switzerland). 2020;(23)
Abstract
Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in industrialized parts of the world, adding to natural occurrence and causing environmental and health concerns. A vast amount of data shows that metal may accumulate in the human body and its deposition has been detected in organs such as brain and liver. Moreover, the disease nephrogenic systemic fibrosis has been linked to increased Gd3+ levels. Investigation of Gd3+ effects at the cellular and molecular levels mostly revolves around calcium-dependent proteins, since Gd3+ competes with calcium due to their similar size; other reports focus on interaction of Gd3+ with nucleic acids and carbohydrates. However, little is known about Gd3+ effects on membranes; yet some results suggest that Gd3+ interacts strongly with biologically-relevant lipids (e.g., brain membrane constituents) and causes serious structural changes including enhanced membrane rigidity and propensity for lipid fusion and aggregation at much lower concentrations than other ions, both toxic and essential. This review surveys the impact of the anthropogenic use of Gd emphasizing health risks and discussing debilitating effects of Gd3+ on cell membrane organization that may lead to deleterious health consequences.
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10.
Copper Depletion as a Therapeutic Strategy in Cancer.
Lopez, J, Ramchandani, D, Vahdat, L
Metal ions in life sciences. 2019
Abstract
Copper is an essential trace element that plays a critical role in a variety of basic biological functions, and serves as a key component in a number of copper-dependent enzymes that regulate such processes as cell proliferation, angiogenesis, and motility. A growing body of preclinical work has demonstrated that copper is essential to metastatic cancer progression, and may have a role in tumor growth, epithelial-mesenchymal transition, and the formation of the tumor microenvironment and pre-metastatic niche. As a result, copper depletion has emerged as a novel therapeutic strategy in the treatment of metastatic cancer. We present a review of the physiologic role of copper with a discussion of relevant enzymes of the copper proteome in both normal tissue and in cancer. We conducted a comprehensive review of the available preclinical data of several copper chelation agents, including penicillamine, trientine, disulfiram, clioquinol, and tetrathiomolybdate (TM), across a variety of tumor types. We also present the existing early phase clinical trial data for the use of the copper chelator TM in the treatment of breast cancer and other malignancies.