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Micromachines Jan 2024D-penicillamine (D-PA) is a sulfur-containing drug that has been used for various health conditions. However, like any medication, overdosing on D-PA can have adverse...
D-penicillamine (D-PA) is a sulfur-containing drug that has been used for various health conditions. However, like any medication, overdosing on D-PA can have adverse effects and may require additional treatment. Therefore, developing simple and sensitive methods for sensing D-PA can play a crucial role in improving its efficacy and reducing its side effects. Sensing technologies, such as electrochemical sensors, can enable accurate and real-time measurement of D-PA concentrations. In this work, we developed a novel electrochemical sensor for detecting D-PA by modifying a carbon paste electrode (CPE) with a multi-walled carbon nanotube-CoO nanocomposite, benzoyl-ferrocene (BF), and ionic liquid (IL) (MWCNT-CoO/BF/ILCPE). Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry (CHA) were employed to explore the electrochemical response of D-PA on the developed sensor, the results of which verified a commendable electrochemical performance towards D-PA. Under optimized conditions, the developed sensor demonstrated a rapid response to D-PA with a linear dynamic range of 0.05 μM-100.0 μM, a low detection limit of 0.015 μM, and a considerable sensitivity of 0.179 μA μM. Also, the repeatability, stability, and reproducibility of the MWCNT-CoO/BF/ILCPE sensor were studied and showed good characteristics. In addition, the detection of D-PA in pharmaceutical and biological matrices yielded satisfactory recoveries and relative standard deviation (RSD) values.
PubMed: 38398949
DOI: 10.3390/mi15020220 -
Journal of Nanobiotechnology Feb 2024The formation of blood vessel system under a relatively higher Cu ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in...
The formation of blood vessel system under a relatively higher Cu ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.
Topics: Humans; Phototherapy; Copper; Fluorescence; Hyperthermia, Induced; Neoplasms; Ions; Cell Line, Tumor; Nanoparticles; Tumor Microenvironment
PubMed: 38374027
DOI: 10.1186/s12951-024-02343-5 -
BMC Neurology Jan 2024Wilson's disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles... (Review)
Review
BACKGROUND
Wilson's disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence.
CASE PRESENTATION
The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson's disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson's disease combined with intracranial lipoma and corpus callosum dysplasia. The patient's WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient's abnormal copper metabolism may promote the growth of intracranial lipoma.
CONCLUSION
The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases' more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.
Topics: Pregnancy; Humans; Female; Hepatolenticular Degeneration; Corpus Callosum; Copper; Penicillamine; Lipoma; Brain Neoplasms
PubMed: 38273263
DOI: 10.1186/s12883-024-03541-2 -
Cureus Dec 2023Wilson's disease (WD) is an autosomal recessive disorder affecting the metabolism of copper that can present with a variety of clinical symptoms. Low levels of serum...
Wilson's disease (WD) is an autosomal recessive disorder affecting the metabolism of copper that can present with a variety of clinical symptoms. Low levels of serum copper and ceruloplasmin, increased excretion of copper in the urine, and/or increasing quantities of copper in the liver are diagnostic indicators. The gold standard for diagnosis is genetic testing. The care approach includes the utilization of liver transplants as a therapeutic option in advanced patients and the use of copper-chelating medications. We describe a unique case of WD in a 14-year-old girl who presented with ascites, hemolytic anemia, and liver dysfunction. There was no indication of abdominal TB, and her viral, autoimmune, and hemolytic profiles were all normal. Low serum ceruloplasmin, elevated urine copper, and distinctive liver histology all supported the WD diagnosis. After starting penicillamine medication, the patient's symptoms improved, but her blood counts did not. This example emphasizes how crucial it is to rule out WD in patients with chronic liver disease, hemolytic anemia, and unexplained ascites, particularly in younger age groups.
PubMed: 38234952
DOI: 10.7759/cureus.50724 -
BioMed Research International 2024[This retracts the article DOI: 10.1155/2022/3619308.].
[This retracts the article DOI: 10.1155/2022/3619308.].
PubMed: 38230034
DOI: 10.1155/2024/9810690 -
Heliyon Jan 2024It is well known that the chiral materials combined with metal ion's structure have been identified as promising candidate for the nursing Alzheimer Disease (AD)...
Novel fabrication of Cu(II)-incorporated chiral d-penicillamine-chitosan nanocomposites enantio-selectively inhibit the induced amyloid β aggregation for Alzheimer's disease therapy.
It is well known that the chiral materials combined with metal ion's structure have been identified as promising candidate for the nursing Alzheimer Disease (AD) treatment, particularly to inhibit amyloid (Aβ) due to their significant pharmacological effect on the living bodies. In the present study, Cu(II)/Chitosan nanocomposite caped with chiral penicillamine (Cu@D-PEN/Chitosan) have been synthesized and used as an effective amyloid-β (Aβ) inhibitor. The composite formations of the samples were confirmed from the FTIR and XRD, studies. FE-SEM, TEM and AFM studies have been carried out to depict the morphological analysis of the nanocomposites. The prepared samples have also been subjected to various studies such as encapsulation efficiency, drug loading capacity, drug release and biodegrading or compatibility of the nanocomposites to support the Aβ aggregation inhibiting ability investigations. It was observed that the increase in the concentration of the Cu@D-PEN/Chitosan enhancing the Aβ inhibiting ability. Thus, the Cu(II)@D-PEN/Chitosan showed improving memory effect suggesting that Cu(II)@D-PEN/Chitosan nanocomposites may be a potential candidate for inhibiting the Aβ aggregation in nursing AD treatment.
PubMed: 38223723
DOI: 10.1016/j.heliyon.2023.e23563 -
JPMA. the Journal of the Pakistan... Jan 2024Wilson's disease is arare inherited disorder of copper met abolism. If le f t untre ated, i t can turn into a multi systemic disease with copper deposition in the liver,...
Wilson's disease is arare inherited disorder of copper met abolism. If le f t untre ated, i t can turn into a multi systemic disease with copper deposition in the liver, brain, a nd other tissues. Diagnosi s of Wilson's is delayed in Pak ist an by many ye a rs on average due to va riabl e presen tations. In ad olescents, the initial s igns a re more likely to b e neuropsychiatric. Here we present a case of Wilso n's disease that pre sented initially with he patic symptoms and did not have signs specific to the di sea s e such as Kayser-Fleischer rings. Our case was diagnosed to be Wilson's Disease on ly on further investigat ions and s ubsequently the patient was treated with chela tion therapy using D-Penicillamine.Wilson's Disease should be kept in mind as a differential diagno sis in adolesce nt patients that present with unexplained acute liver failure and cytopenias without any neurological symptoms, as a missed diagnosis can prove to be fatal.
Topics: Male; Humans; Hepatolenticular Degeneration; Copper; Penicillamine; Brain
PubMed: 38219193
DOI: 10.47391/JPMA.9637 -
Pharmaceutics Dec 2023(1) Background: In patients with Wilson's disease, the deficiency of the copper carrier ATP7B causes the accumulation of copper in the liver, brain and various other...
(1) Background: In patients with Wilson's disease, the deficiency of the copper carrier ATP7B causes the accumulation of copper in the liver, brain and various other organs. Lifelong treatment is therefore mandatory, using copper chelators to increase the excretion of copper and to avoid life-threatening damage. The clinically used reference drug, D-penicillamine, exhibit numerous adverse effects, especially a frequent severe and irreversible neurological worsening, mainly due to its lack of metal selectivity; (2) Methods: A new tetradentate ligand based on an 8-aminoquinoline entity, named TDMQ20, which is highly selective for copper compared with other metal ions, is evaluated in "toxic milk" TX mice as an oral treatment of this Wilson's disease murine model; (3) Results: The concentration of copper in the liver of "toxic milk" TX mice decreased and the fecal excretion of copper increased upon oral treatment with TDMQ20. Both effects are dose-dependent, and more pronounced than those of D-penicillamine; (4) Conclusions: The TDMQ20 copper chelator is more efficient than the reference drug D-penicillamine for the treatment of a Wilson's disease murine model. Pharmacological data obtained with TDMQ20 on the TX mouse model strongly support the selection of this ligand as a drug candidate for this genetic disease.
PubMed: 38140060
DOI: 10.3390/pharmaceutics15122719 -
Hepatology (Baltimore, Md.) May 2024Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of...
BACKGROUND AND AIMS
Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN. We tested whether TRI and/or PEN also inhibit intestinal copper absorption.
APPROACH AND RESULTS
Sixteen healthy volunteers were examined with positron emission tomography (PET)/CT 1 and 15 hours after an oral Copper-64 ( 64 Cu) dose. They then received 7 days of either PEN or TRI (trientine tetrahydrochloride), after which the 64 Cu PET/CT scans were repeated. Venous blood samples were also collected. Pretreatment to posttreatment changes of the hepatic 64 Cu uptake reflect the effect of drugs on intestinal absorption. 64 Cu activity was normalized to dose and body weight and expressed as the mean standard uptake value. TRI (n=8) reduced hepatic 64 Cu activity 1 hour after 64 Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p <0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p <0.02, indicating strong inhibition of intestinal 64 Cu absorption. PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p <0.04.
CONCLUSIONS
In this mechanistic study, we show that TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal copper absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI. The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.
Topics: Humans; Penicillamine; Trientine; Copper; Positron Emission Tomography Computed Tomography; Copper Radioisotopes; Hepatolenticular Degeneration; Positron-Emission Tomography
PubMed: 38088886
DOI: 10.1097/HEP.0000000000000708 -
World Journal of Hepatology Oct 2023Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q. This leads to copper deposition in various organs, most importantly... (Review)
Review
Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q. This leads to copper deposition in various organs, most importantly in the liver and brain. The genetic mutations are vast, well reported in the West but poorly documented in developing countries. Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians. Diagnostic scoring systems are not fool-proof. The availability and affordability of chelators in developing countries impact the drug compliance of patients. While D-penicillamine is a potent drug, its side effects lead to drug discontinuation. Trientine is cost-prohibitive in developing countries. There is no single test to assess the adequacy of chelation. Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool. In the presence of cirrhosis, hypersplenism clouds the assessment of myelosuppression of drugs. Similarly, it may be difficult to distinguish disease tubulopathy from drug-induced glomerulonephritis. Neurological worsening due to chelators may appear similar to disease progression. Presentation as fulminant hepatic failure requires rapid workup. There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices. This review addresses the challenges and clinical dilemmas faced at beside in developing countries.
PubMed: 37970614
DOI: 10.4254/wjh.v15.i10.1109