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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 -
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 -
ACS Applied Bio Materials May 2024Bacterial biofilms play a central role in the development and progression of periodontitis, a chronic inflammatory condition that affects the oral cavity. One solution...
Bacterial biofilms play a central role in the development and progression of periodontitis, a chronic inflammatory condition that affects the oral cavity. One solution to current treatment constraints is using nitric oxide (NO)─with inherent antimicrobial properties. In this study, an antimicrobial coating is developed from the NO donor -nitroso--acetylpenicillamine (SNAP) embedded within polyethylene glycol (PEG) to prevent periodontitis. The SNAP-PEG coating design enabled a controlled NO release, achieving tunable NO levels for more than 24 h. Testing the SNAP-PEG composite on dental floss showed its effectiveness as a uniform and bioactive coating. The coating exhibited antibacterial properties against and , with inhibition zones measuring up to 7.50 ± 0.28 and 14.80 ± 0.46 mm, respectively. Furthermore, SNAP-PEG coating materials were found to be stable when stored at room temperature, with 93.65% of SNAP remaining after 28 d. The coatings were biocompatible against HGF and hFOB 1.19 cells through a 24 h controlled release study. This study presents a facile method to utilize controlled NO release with dental antimicrobial coatings comprising SNAP-PEG. This coating can be easily applied to various substrates, providing a user-friendly approach for targeted self-care in managing gingival infections associated with periodontitis.
Topics: Streptococcus mutans; Nitric Oxide; Escherichia coli; Humans; Anti-Bacterial Agents; Materials Testing; Coated Materials, Biocompatible; Polyethylene Glycols; Microbial Sensitivity Tests; Particle Size; Biofilms; S-Nitroso-N-Acetylpenicillamine; Surface Properties; Periodontitis; Gingiva
PubMed: 38593411
DOI: 10.1021/acsabm.4c00051 -
Food Chemistry Aug 2023Seafood is highly perishable and monitoring its freshness this thus an important issue. For the first time, the current study developed a dual-mode freshness indicator...
Seafood is highly perishable and monitoring its freshness this thus an important issue. For the first time, the current study developed a dual-mode freshness indicator based on d-penicillamine capped bimetallic gold/copper nanoclusters (DPA-Au/CuNCs) as a response probe for simultaneous monitoring of ammonia and temperatures to assess seafood freshness. Results indicated that the prepared DPA-Au/CuNCs have good sensitivity toward ammonia, with a limit of detection of 0.14 ppm. The indicator as a gas sensor for ammonia vapour detection exhibited highly recognizable fluorescence colour changes and the variations from white to yellow were observed with increasing storage temperature under natural light. For confirming its practical applications, the indicator was used to simultaneously monitor ammonia and temperatures during the storage of shrimp and fish, showing good potential for practical applications in evaluating seafood freshness for the food industry.
Topics: Animals; Ammonia; Fishes; Product Packaging; Seafood; Temperature; Copper; Gold; Nanostructures
PubMed: 37001353
DOI: 10.1016/j.foodchem.2023.135929 -
BMJ Open Gastroenterology Aug 2023Wilson's disease (WD) is a copper metabolism disorder characterised by a progressive accumulation of this metal mainly in the liver and the brain. Treatment is based on...
INTRODUCTION
Wilson's disease (WD) is a copper metabolism disorder characterised by a progressive accumulation of this metal mainly in the liver and the brain. Treatment is based on the removal of copper operated by the chelators, among which, D-penicillamine (DP) is prescribed as a first-line treatment in most situations. There is some evidence in linking the use of DP with a risk of vitamin B; therefore, vitamin supplementation is sometimes recommended, although non-consensually. The objective of our study was to evaluate the level of vitamin B in WD patients treated with DP with and without associated supplementation.
METHODOLOGY
All WD patients followed at the National Reference Centre for WD in Lyon between January 2019 and December 2020 treated with DP for more than 1 year were included and separated in two groups according to vitamin B supplementation. The level of vitamin B was measured by the determination of pyridoxal phosphate (PLP).
RESULTS
A total of 37 patients were included. Average age of 23.3±14.8 years, 15 patients with <18 years. Median duration of treatment was 51 (55.8) months. 15 patients were under vitamin B supplementation and 22 had interrupted it for more than 1 year. The median PLP level was significantly higher in the group with supplementation, 137.2 (86.7) nmol/L vs 64.9 (30.8) nmol/(p<0.01). No patient had a PLP level<35 nmol/L.
CONCLUSION
Long-term stable WD patients under DP treatment probably do not need vitamin B supplementation.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Vitamin B 6; Hepatolenticular Degeneration; Penicillamine; Copper; Dietary Supplements; Vitamins
PubMed: 37652551
DOI: 10.1136/bmjgast-2023-001211 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Mar 2024To investigate the neuroprotective effect of Capsule (HPTQ) in a rat model of Wilson disease (WD) and explore the underlying mechanisms.
OBJECTIVE
To investigate the neuroprotective effect of Capsule (HPTQ) in a rat model of Wilson disease (WD) and explore the underlying mechanisms.
METHODS
SD rat models of WD were established by feeding of coppersupplemented chow diet and drinking water for 12 weeks, and starting from the 9th week, the rats were treated with low-, moderate- and high-dose HPTQ, penicillamine, or normal saline by gavage on a daily basis for 3 weeks. Copper levels in the liver and 24-h urine of the rats were detected, and their learning and memory abilities were evaluated using Morris water maze test. HE staining was used to observe morphological changes of CA1 region neurons in the hippocampus, and neuronal apoptosis was detected with TUNEL staining. Hippocampal expressions of endoplasmic reticulum stress (ERS)-mediated apoptosis pathway-related proteins GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 at both the mRNA and protein levels were detected using RT-qPCR, immunofluorescence assay or Western blotting.
RESULTS
Compared with normal control rats, the rat models with copper overload-induced WD exhibited significantly increased copper levels in both the liver and 24-h urine, impaired learning and memory abilities, obvious hippocampal neuronal damage in the CA1 region and increased TUNEL-positive neurons (<0.01), with also lowered mRNA and protein expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the hippocampus (all <0.01). Treatments with HPTQ and penicillamine significantly lowered copper level in the liver but increased urinary copper level, improved learning and memory ability, alleviated neuronal damage and apoptosis in the hippocampus, and decreased hippocampal expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the rat models (<0.01 or 0.05).
CONCLUSION
HPTQ Capsule has neuroprotective effects in rat models of WD possibly by inhibiting ERS-mediated apoptosis pathway.
Topics: Rats; Animals; Rats, Sprague-Dawley; Hepatolenticular Degeneration; Caspase 3; Caspase 9; Caspase 12; Copper; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Apoptosis; Hippocampus; Apoptosis Regulatory Proteins; Penicillamine; Cognitive Dysfunction; RNA, Messenger
PubMed: 38597435
DOI: 10.12122/j.issn.1673-4254.2024.03.05 -
Proceedings of the National Academy of... Mar 2024The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics....
The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad-spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. penicillamine-stabilized NPs with left-handed curved apexes display half-maximal inhibitory concentrations (IC) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments.
Topics: Humans; Animals; Mice; SARS-CoV-2; COVID-19; Coronavirus OC43, Human; Antibodies; Antiviral Agents
PubMed: 38502692
DOI: 10.1073/pnas.2310469121 -
BMC Pediatrics Apr 2024Systemic lupus erythematosus (SLE) and Wilson's disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is... (Review)
Review
BACKGROUND
Systemic lupus erythematosus (SLE) and Wilson's disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose.
CASE REPORT
We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery.
CONCLUSIONS
SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.
Topics: Child; Female; Humans; Ceruloplasmin; Copper; Hepatolenticular Degeneration; Lupus Erythematosus, Systemic; Penicillamine
PubMed: 38622515
DOI: 10.1186/s12887-024-04713-2 -
Life (Basel, Switzerland) Aug 2023Wilson's disease (WD) is a genetic disorder with copper accumulation in various tissues leading to related clinical symptoms (mainly hepatic and neuropsychiatric) which...
Wilson's disease (WD) is a genetic disorder with copper accumulation in various tissues leading to related clinical symptoms (mainly hepatic and neuropsychiatric) which can be in 85% of patients successfully treated with anti-copper agents. However, during WD treatment neurological deterioration may occur in several patients. D-penicillamine (DPA) is one of the most frequently used drugs in WD treatment. Despite its efficacy, DPA can produce many adverse drug reactions, which should be recognized early. We present the case of a 51-year-old man diagnosed with the hepatic form of WD and initially treated with DPA in whom after 15 months of treatment, diplopia and evening ptosis occurred. WD treatment non-compliance as well as overtreatment were excluded. Supported by neurological symptoms, a positive edrophonium test, and high serum levels of antibodies against acetylcholine receptors (AChR-Abs), as well as low concentrations of antibodies against muscle-specific kinase (MuSK-Abs), the diagnosis of myasthenia gravis (MG), induced by DPA, was established. DPA was stopped; zinc sulfate for WD and pyridostigmine for MG symptoms were introduced. Diplopia and ptosis subsided after a few days, which supported our diagnosis. During a follow-up visit after 6 months, the patient did not present any MG symptoms. AChR-Abs level gradually decreased and MuSK-Abs were no longer detected. Pyridostigmine was stopped, and within 9 months of follow-up, the neurological symptoms of MG did not reoccur. The authors discussed the patient's neurological deterioration, performed a systematic review of DPA-induced MG in WD and concluded that MG is a rare and usually reversible complication of DPA treatment. DPA-induced MG generally occurs 2-12 months after treatment initiation and ocular symptoms predominate. Response to pyridostigmine treatment is good and MG symptoms usually reverse within one year after DPA treatment cessation. However, symptoms may persist in some cases where DPA treatment is only a trigger factor for MG occurrence.
PubMed: 37629572
DOI: 10.3390/life13081715 -
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