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Current Problems in Pediatric and... Feb 2020Cases of severe childhood lead poisoning (a blood lead level (BLL) ≥45 mcg/dL) in the United States have decreased with time. Clinicians will encounter such cases...
Cases of severe childhood lead poisoning (a blood lead level (BLL) ≥45 mcg/dL) in the United States have decreased with time. Clinicians will encounter such cases only rarely. When such cases arise, however, recognizing their complexities and identifying resources that can help in management are important. We present here a case of severe childhood lead poisoning, highlighting the variable presentation, the rebound phenomenon of BLL after chelation, the usefulness of the zinc protoporphyrin as an adjunctive monitoring parameter, and the importance of early involvement of an inter-professional team.
Topics: Chelating Agents; Child, Preschool; Dimercaprol; Female; Hospitalization; Humans; Lead Poisoning; Massachusetts
PubMed: 32122813
DOI: 10.1016/j.cppeds.2020.100757 -
Journal of Neurology Jun 2020A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal... (Comparative Study)
Comparative Study Randomized Controlled Trial
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.
Topics: Adolescent; Adult; Chelating Agents; Copper; Female; Globus Pallidus; Hepatolenticular Degeneration; Humans; Magnetic Resonance Imaging; Male; Outcome Assessment, Health Care; Penicillamine; Substantia Nigra; Unithiol; Young Adult
PubMed: 32060651
DOI: 10.1007/s00415-020-09746-y -
Biomolecules Feb 2020High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of... (Review)
Review
High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.
Topics: Animals; Antidotes; Arsenic; Arsenic Poisoning; Arsenicals; Chelating Agents; Dimercaprol; Drinking Water; Humans; Models, Molecular; Occupational Exposure; Oxidative Stress; Succimer; Unithiol; Water Pollutants, Chemical
PubMed: 32033229
DOI: 10.3390/biom10020235 -
Protein and Peptide Letters 2020Ionic complementary peptide EAK-16 has been studies for anticancer drug delivery application. This is a 16 residues, short sequence peptide has ability to trosnform into...
BACKGROUND
Ionic complementary peptide EAK-16 has been studies for anticancer drug delivery application. This is a 16 residues, short sequence peptide has ability to trosnform into micro/nanoparticle via self-assembly. However, it is still not clear that how this can bind with cell membrane to induce membrane leakage or delivering their cargo inside cell membrane.
OBJECTIVE
The main objective of this work was to understand behaviour of secondary structure conformation of peptide in solution and at lipid membrane interfaces and membrane permeability of synthetic ionic complementary peptide EAK-16. The corresponding secondary structure conformation was evaluated.
METHODS
We performed biophysical investigation to probe the interaction of synthesised ionic complementary peptide (EAK-16) with dimyristoylphospholcholine (DMPC) and dimyristoylphosphoserine (DMPS) membrane interfaces. The folding behaviours of EAK-16 were studied with Circular Dichroism (CD) spectroscopy. Membrane leakage with peptide was confirmed with calcein leakage assay.
RESULTS
Our finding of this study showed that in aqueous phase EAK-16 was predominantly folded into β-sheets. The temperature could alter the β-sheets. However, in DMPC and DMPS membrane interfaces, EAK-16 adopted helical conformation. EAK-16 has preference in perturbing anionic compared Zwitterionic lipid vesicles. This study proposed that hydrophobic grooves of EAK-16 might be a key in the association with lipid bilayers. Secondly, a charge distribution of ionic residues would also support the orientation at lipid bilayers. This peptide membrane association would facilitate the membrane destabilisation.
CONCLUSION
This study demonstrated the supporting evidence that EAK-16 could interact with lipid membranes and conforming to helical structure, while the helical conformation induced the lipid membrane leakage. Overall, this study provides a physical rationale that ionic complementary peptide can be a useful tool for designing and development of novel antibiotics and anticancer agents along its previous drug delivery applications.
Topics: Dimyristoylphosphatidylcholine; Lipid Bilayers; Peptides; Protein Conformation, beta-Strand; Unithiol
PubMed: 32003653
DOI: 10.2174/0929866527666200129141116 -
The Turkish Journal of Pediatrics 2019Çelebi-Tayfur A, Yaradılmış RM, Ulus F, Çaltık-Yılmaz A, Özayar E, Koşar B, Büyükkaragöz B, Horasanlı E. Bismuth intoxication resulting in acute kidney...
Çelebi-Tayfur A, Yaradılmış RM, Ulus F, Çaltık-Yılmaz A, Özayar E, Koşar B, Büyükkaragöz B, Horasanlı E. Bismuth intoxication resulting in acute kidney injury in a pregnant adolescent girl. Turk J Pediatr 2019; 61: 292-296. Bismuth intoxication is a rare cause of acute kidney injury (AKI) and is usually reversible by appropriate therapeutic measures. We present here a case of an adolescent pregnant girl who developed AKI due to an overdose of colloidal bismuth subcitrate (CBS, total amount of 6 g). She received parenteral chelating agent dimercaprol for 14 days. Continuous venovenous hemodiafiltration (CVVHD) with high-flux membrane was carried out in the first 3 days of chelating therapy and intermittent hemodialysis for 11 days, thereafter. The patient recovered clinically and was discharged after 21 days. She gave birth to a healthy term boy. At the last visit, the baby was 6 months old with normal growth and development as well as normal kidney functions. Neither deterioration in renal functions nor emergence of proteinuria was recorded in the patient during follow-up care after hospital discharge. In cases of AKI due to an overdose of CBS, treatment with dimercaprol combined with high flux hemodiafiltration and subsequently hemodialysis appears to be both useful and safe for bismuth elimination.
Topics: Acute Kidney Injury; Adolescent; Bismuth; Drug Overdose; Female; Hemodiafiltration; Humans; Pregnancy; Pregnancy Complications; Renal Dialysis
PubMed: 31951346
DOI: 10.24953/turkjped.2019.02.024 -
BMC Nephrology Oct 2019Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical... (Review)
Review
BACKGROUND
Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical practice in this area is rather scattered.
CASE PRESENTATION
We present a case of symptomatic lead and arsenic poisoning from use of Ayurvedic medicine in a 28-year-old man with end-stage kidney disease on chronic hemodialysis. We describe his treatment course with chelating agents and extracorporeal blood purification, and review the relevant literature to provide general guidance.
CONCLUSION
Cumulative clinical experience assists in identifying preferred chelators and modalities of extracorporeal blood purification when managing such patients. However, a larger body of real-world or clinical trial evidence is necessary to inform evidence-based guidelines for the management of heavy metal poisoning in anuric patients.
Topics: Adult; Animals; Anuria; Arsenic Poisoning; Chelating Agents; Continuous Renal Replacement Therapy; Dimercaprol; Edetic Acid; Humans; Kidney Failure, Chronic; Lead Poisoning; Male; Renal Dialysis; Succimer; Unithiol
PubMed: 31623560
DOI: 10.1186/s12882-019-1561-1 -
The American Journal of Gastroenterology Aug 2019
Topics: Arsenic Poisoning; Arsenicals; Burns, Chemical; Chelating Agents; Chlorides; Dimercaprol; Gastric Lavage; Gastric Mucosa; Gastroscopy; Humans; Male; Middle Aged
PubMed: 30946039
DOI: 10.14309/ajg.0000000000000194 -
The Journal of Emergency Medicine Mar 2019Mercury poisoning is an uncommon diagnosis in the United States, but it is a differential diagnosis that physicians should consider because it can lead to potentially...
BACKGROUND
Mercury poisoning is an uncommon diagnosis in the United States, but it is a differential diagnosis that physicians should consider because it can lead to potentially fatal complications if untreated. Due to the nonspecific presentation of mercury poisoning, which includes symptoms such as fever, nausea, vomiting, and abdominal pain, misdiagnosis may occur unless a proper history is taken.
CASE REPORT
In the present case, a white female patient was misdiagnosed repeatedly with a viral illness and sent home from the local hospital. The patient presented with a diffuse full-body rash, fever, myalgias, headache, peripheral neuropathy, oral paresthesias, and tender cervical posterior lymphadenopathy. After obtaining a thorough history, it was discovered that the patient and her family were exposed to mercury through a spill of elemental mercury in their home. Blood mercury levels in the patient were 170 ng/mL. The patient was treated with a course of dimercaprol. Her symptoms improved and she was discharged on hospital day 5. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ultimately, mercury poisoning is a treatable condition, but if exposure continues and the patient is not treated, it may lead to complications such as severe pneumonitis, renal tubular necrosis, and neurological dysfunction. In some instances, neurological symptoms may persist even if the source of exposure is removed. For these reasons, recognition and prompt treatment after a suspected exposure is important.
Topics: Adult; Chelating Agents; Chelation Therapy; Emergency Service, Hospital; Environmental Exposure; Exanthema; Female; Fever; Humans; Mercury; Mercury Poisoning; Myalgia; Succimer
PubMed: 30718027
DOI: 10.1016/j.jemermed.2018.12.039 -
Medicine Dec 2018Both Wilson disease (WD) and Oculocutaneous Albinism (OCA) are rare autosomal recessive disorders that are caused by mutations on chromosome 13 and chromosome 11,...
RATIONALE
Both Wilson disease (WD) and Oculocutaneous Albinism (OCA) are rare autosomal recessive disorders that are caused by mutations on chromosome 13 and chromosome 11, respectively. Here, we report on a patient with coexisting WD and OCA, initially presenting episodes of tremors.
PATIENT CONCERNS
WD is a disorder of copper metabolism. The main sites of copper accumulation are the liver and the brain, resulting in hepatic symptoms. OCA is a disorder of melanin biosynthesis, characterized by a generalized reduction in pigmentation of the eyes (oculo-), skin (-cutaneous), and hair.
DIAGNOSIS
The diagnosis of WD was confirmed by neurological symptoms, metabolism tests, and MRI scans. Interestingly, the patient also had very light skin color, blond hair and eyebrows, and dark brown eyelashes and irises. Because the association of dermatologic signs in WD has rarely been reported, OCA was highly suspected based on these clinical findings. Genetic analysis was subsequently conducted, and the results revealed the p. (Arg778Leu) mutation in 1 allele and the p. (Asn1270Ser) mutation in the other allele of the ATP7B gene, confirming the diagnosis of WD; the p. (D456fs) mutation in 1 allele and the p. (R299H) mutation in the other allele of the TYR gene, confirming the diagnosis of OCA. The family history was positive for WD with a 14-year-old younger brother also being diagnosed with it. Her parents are negative for OCA and WD.
INTERVENTIONS
Sodium dimercaptopropanesulfonate (DMPS) was given during hospitalization. D-penicillamine and zinc sulfate treatment was initiated after discharge for long-term control.
OUTCOMES
Postural and intention tremor disappeared, and other symptoms and signs markedly improved after treatment.
LESSONS
In this study, we reported on the first case of a child who simultaneously presented WD and OCA, bringing up the possibility of a presumable link between these 2 rare diseases.
Topics: Albinism, Oculocutaneous; Asian People; Astringents; Chelating Agents; Female; Hepatolenticular Degeneration; Humans; Magnetic Resonance Imaging; Mutation; Penicillamine; Treatment Outcome; Unithiol; Young Adult; Zinc Sulfate
PubMed: 30558096
DOI: 10.1097/MD.0000000000013744 -
Bioorganic & Medicinal Chemistry Letters Jan 2019Reported herein is a fluorescence assay for the rapid screening of metallo-β-lactamase (MBL) inhibitors. This assay employs a fluorogenic carbapenem CPC-1 as substrate...
Reported herein is a fluorescence assay for the rapid screening of metallo-β-lactamase (MBL) inhibitors. This assay employs a fluorogenic carbapenem CPC-1 as substrate and is compatible with all MBLs, including B1, B2 and B3 subclass MBLs. The efficiency of this assay was demonstrated by the rapid inhibition screening of a number of molecules against B2 MBL CphA and 2,3-dimercaprol was identified as a potent CphA inhibitor.
Topics: Carbapenems; Dose-Response Relationship, Drug; Fluorescence; Fluorescent Dyes; Humans; Molecular Structure; Structure-Activity Relationship; beta-Lactamase Inhibitors; beta-Lactamases
PubMed: 30470495
DOI: 10.1016/j.bmcl.2018.11.025