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Drug Discovery Today Jul 2023This report discusses potential therapies for treating human coronaviruses (HCoVs) and their economic impact. Specifically, we explore therapeutics that can support the... (Review)
Review
This report discusses potential therapies for treating human coronaviruses (HCoVs) and their economic impact. Specifically, we explore therapeutics that can support the body's immune response, including immunoglobulin (Ig)A, IgG and T-cell responses, to inhibit the viral replication cycle and improve respiratory function. We hypothesize that carbon quantum dots conjugated with S-nitroso-N-acetylpenicillamine (SNAP) could be a synergistic alternative cure for treating respiratory injuries caused by HCoV infections. To achieve this, we propose developing aerosol sprays containing SNAP moieties that release nitric oxide and are conjugated onto promising nanostructured materials. These sprays could combat HCoVs by inhibiting viral replication and improving respiratory function. Furthermore, they could potentially provide other benefits, such as providing novel possibilities for nasal vaccines in the future.
Topics: Humans; S-Nitroso-N-Acetylpenicillamine; Nitric Oxide; Virus Replication
PubMed: 37119964
DOI: 10.1016/j.drudis.2023.103601 -
World Journal of Clinical Cases May 2022Wilson's disease (WD) is a rare inherited disorder of human copper metabolism, with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and... (Review)
Review
Wilson's disease (WD) is a rare inherited disorder of human copper metabolism, with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations. In healthy individuals, the bile is the main route of elimination of copper. In WD patients, copper accumulates in the liver, it is released into the bloodstream, and is excreted in urine. Copper can also be accumulated in the brain, kidneys, heart, and osseous matter and causes damage due to direct toxicity or oxidative stress. Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood. Adherent, non-cirrhotic WD patients seem to have a normal life expectancy. Nevertheless, chronic management of patients with Wilson's disease is challenging, as available biochemical tests have many limitations and do not allow a clear identification of non-compliance, overtreatment, or treatment goals. To provide optimal care, clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment. The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD. In particular, it summarises current knowledge on Wilson's disease clinical and biochemical monitoring and treatment. It also analyses available evidence on pregnancy and the role of low-copper diet in WD. Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.
PubMed: 35663095
DOI: 10.12998/wjcc.v10.i14.4334 -
Fetal and Pediatric Pathology Oct 2022To evaluate and compare pregnancy outcomes in women with Wilson's disease (WD) undergoing different therapies during pregnancy.
OBJECTIVES
To evaluate and compare pregnancy outcomes in women with Wilson's disease (WD) undergoing different therapies during pregnancy.
MATERIAL AND METHODS
Retrospective review of medication in WD patients during pregnancy and the outcomes.
RESULTS
Of 26 pregnancies, zinc was used in 14 (53.8%), D-penicillamine in 4 (15.4%) patients, and 8 (30.8%) were untreated. Spontaneous abortion was observed in 8 (30.8%) pregnancies - untreated patients (4/8 pregnancies), zinc (2/14 pregnancies) and D-penicillamine (2/4 pregnancies) -, healthy outcome in 12 (46.1%) and birth defects in 6 (23.1%). All cases of birth defects occurred in patients using zinc therapy (6/14 pregnancies).
CONCLUSIONS
A remarkably high frequency of fetal complications shed lights on the potentially harmful effect of WD drugs during childbearing age. Zinc's safety profile may have to be better evaluated during pregnancy, as all of birth defects occurred with zinc therapy.
Topics: Abortion, Spontaneous; Female; Hepatolenticular Degeneration; Humans; Penicillamine; Pregnancy; Pregnancy Outcome; Zinc
PubMed: 34350816
DOI: 10.1080/15513815.2021.1960940 -
Scandinavian Journal of Gastroenterology Jan 2020Gastrointestinal symptoms are common in patients with Wilson disease (WD) and may be related to the disease itself or to adverse drug reactions (ADRs). To investigate...
Gastrointestinal symptoms are common in patients with Wilson disease (WD) and may be related to the disease itself or to adverse drug reactions (ADRs). To investigate gastroscopy findings in patients with WD and to analyze the risk of gastropathy in the context of different manifestations and treatments of WD as well as infection status. This cross-sectional study included patients diagnosed or monitored for WD between 2007 and 2017. All enrolled patients were examined with gastroscopy and checked for infection with a urease test. Based on predominant manifestations, WD was classified as pre-symptomatic, hepatic (only liver symptoms) or neurological. Patients were divided into three treatment groups: untreated, treated with d-penicillamine (DPA) or zinc sulfate therapy. Of 115 patients, 58 were male and the median age was 30 years. Gastropathy was observed in 65.2% of all patients. Factors that increased the risk of gastropathy were zinc sulfate (odds ratio [OR] = 3.01; 95% confidence interval [CI]: 1.12-8.09, = .03), infection (OR = 2.96; 95%CI: 1.34-6.56, = .01) and neurological manifestations (OR = 2.55; 95%CI: 1.16-5.60, = .02). In total, 9.6% of patients had gastric or duodenal ulcers and 29.6% had esophageal varices but no difference was seen by treatment status. In multivariate analysis, zinc sulfate remained associated with higher risk of gastropathy compared with no treatment (OR = 4.57; 95%CI: 1.21-17.19; = .03) and DPA (OR = 6.28; 95%CI: 1.43-27.56; = .01). Our results show that gastropathy in WD may be influenced by the treatment used.KeypointsIn a retrospective study of 115 patients with Wilson's disease, gastric injury was frequent.Patients receiving zinc sulfate had increased gastropathy risk compared with those receiving no treatment or d-penicillamine.
Topics: Adult; Cross-Sectional Studies; Esophageal and Gastric Varices; Female; Helicobacter Infections; Hepatolenticular Degeneration; Humans; Logistic Models; Male; Middle Aged; Penicillamine; Peptic Ulcer; Poland; Retrospective Studies; Risk; Young Adult; Zinc Sulfate
PubMed: 31865812
DOI: 10.1080/00365521.2019.1703035 -
Cureus Jul 2023Wilson's disease (WD) is an inherited disorder characterized by the accumulation of copper in various organs, particularly the liver, central nervous system, and cornea....
Wilson's disease (WD) is an inherited disorder characterized by the accumulation of copper in various organs, particularly the liver, central nervous system, and cornea. The clinical presentation of WD can vary widely. Diagnosis requires a combination of clinical and biochemical findings. We present a case of a 20-year-old woman who presented to the Emergency Room with progressive motor decline. She exhibited characteristic neurological symptoms and signs, such as hypomimia, bradyphrenia, bradykinesia, dysarthria, sialorrhea, upper limb dystonia, and wing-beating tremor. Ophthalmological examination revealed corneal deposits known as Kayser-Fleischer rings. Laboratory investigations demonstrated low levels of ceruloplasmin and elevated serum copper. Brain MRI showed typical signs of copper deposition in the basal ganglia. The Leipzig criteria were used to confirm the diagnosis. Treatment with penicillamine and zinc acetate resulted in symptom improvement. This case highlights the diverse presentation of WD and the importance of early diagnosis and prompt treatment initiation.
PubMed: 37644923
DOI: 10.7759/cureus.42655 -
Proceedings of the National Academy of... Aug 2023Synthetic amorphous silica is a common food additive and a popular cosmetic ingredient. Mesoporous silica particles are also widely studied for their potential use in...
Synthetic amorphous silica is a common food additive and a popular cosmetic ingredient. Mesoporous silica particles are also widely studied for their potential use in drug delivery and imaging applications because of their unique properties, such as tunable pore sizes, large surfaces areas, and assumed biocompatibility. Such a nanomaterial, when consisting of pure silicon dioxide, is generally considered to be chemically inert, but in this study, we showed that oxidation yields for different compounds were facilitated by simply incubating aqueous solutions with pure silica particles. Three thiol-containing molecules, L-cysteine, glutathione, and D-penicillamine, were studied separately, and it was found that more than 95% of oxidation happened after incubating any of these compounds with mesoporous silica particles in the dark for a day at room temperature. Oxidation increased over incubation time, and more oxidation was found for particles having larger surface areas. For nonporous silica particles at submicron ranges, yields of oxidation were different based on the structures of molecules, correlating with steric hindrance while accessing surfaces. We propose that the silyloxy radical (SiO•) on silica surfaces is what facilitates oxidation. Density functional theory calculations were conducted for total energy changes for reactions between different aqueous species and silicon dioxide surfaces. These calculations identified two most plausible pathways of the lowest energy to generate SiO• radicals from water radical cations HO• and hydroxyl radicals •OH, previously known to exist at water interfaces.
PubMed: 37590411
DOI: 10.1073/pnas.2304735120 -
Rinsho Shinkeigaku = Clinical Neurology Sep 2019Wilson disease is an autosomal recessive disorder based on inborn error of copper metabolism. The copper accumulates in the liver, brain, cornea, kidney, and other... (Review)
Review
Wilson disease is an autosomal recessive disorder based on inborn error of copper metabolism. The copper accumulates in the liver, brain, cornea, kidney, and other organs. This disease should be considered any individual with liver abnormality except infant, any patient older than teenage with neurological (especially for extra pyramidal signs) or neuropsychiatric disorder with or without liver disease and sibling of Wilson disease patient. Typically, a combination of low serum ceruloplasmine levels and high levels of urinary copper contents is sufficient to establish a diagnosis. As other diagnostic tests, measurement of hepatic copper content and ATP7B gene analysis are available. The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both copper-chelating agents, such as D-penicillamine or Trientine, and/or zinc acetate. The author recommend zinc acetate monotherapy for mild to moderate hepatic disorder, Trientine mono therapy for mild to moderate neurologic disorder and combination therapy of Trientine and zinc acetate for sever hepatic or neurologic disorder.
Topics: Adolescent; Adult; Biomarkers; Ceruloplasmin; Chelating Agents; Child; Child, Preschool; Copper; Copper-Transporting ATPases; Diagnosis, Differential; Drug Therapy, Combination; Hepatolenticular Degeneration; Humans; Japan; Liver; Middle Aged; Mutation; Penicillamine; Severity of Illness Index; Trientine; Young Adult; Zinc Acetate
PubMed: 31474637
DOI: 10.5692/clinicalneurol.cn-001241 -
Intractable & Rare Diseases Research May 2020Cystine stones are relatively uncommon compared with other stone compositions, constituting just 1% to 2% of adult urinary tract stone diseases, and accounting for up to... (Review)
Review
Cystine stones are relatively uncommon compared with other stone compositions, constituting just 1% to 2% of adult urinary tract stone diseases, and accounting for up to 10% of pediatric stone diseases. Two responsible genes of cystinuria have been identified, the SLC3A1 and the SLC7A9. Cystinuria is diagnosed by family history, stone analysis, or by measurement of urine cystine excretion. Current treatments for cystinuria include increased fluid intake to increase cystine solubility by maintaining daily urine volume of greater than 3 Liter (L). Limiting sodium and protein intake can decrease cystine excretion. When conservative therapy fails, then pharmacologic therapy may be effective. Alkaline urine pH in the 7.0-7.5 range will reduce cystine solubility and can be achieved by the addition of alkali therapy. If these measures fail, cystine-binding thiol drugs such as tiopronin and D-penicillamine are considered. These compounds bind cysteine and prevent the formation of less soluble cystine. These drugs, however, have poor patient compliance due to adverse effects. Captopril can be useful in the treatment of cystine stones but the drug has not been tested in rigorous clinical trials. Novel potential therapies such as alpha-lipoic acid and crystal growth inhibitors (L-cystine dimethyl ester (L-CDME) and L-cystine methyl ester (L-CME)) were developed and tested in animals. Those therapies showed promising results. Compliance with treatment was associated with a lower rate of cystine stone formation.
PubMed: 32494553
DOI: 10.5582/irdr.2020.03006 -
Annals of Indian Academy of Neurology 2022Most centers in developing countries prefer chelation therapy with D-penicillamine for the management of Wilson's disease (WD) because of its easy availability and...
BACKGROUND
Most centers in developing countries prefer chelation therapy with D-penicillamine for the management of Wilson's disease (WD) because of its easy availability and affordability. Neurological worsening following treatment with D-penicillamine is not uncommon. However, there is a paucity of Indian data on the incidence of neurological worsening in children and adolescents with WD following chelation therapy. Our study objectives were to identify the prevalence of neurological worsening in children and adolescents with WD following chelation with D-penicillamine therapy and to describe the management options and outcomes in these patients.
MATERIALS AND METHODS
In this retrospective chart review, children and adolescents with an established diagnosis of WD from 2010 to 2020 were identified from the hospital electronic database. Among these patients, data of children and adolescents with neurological worsening following D-penicillamine therapy were extracted and analyzed.
RESULTS
Neurological worsening was observed in 27/122 (22.1%) children and adolescents with WD on chelation therapy with D-penicillamine. Fifteen patients with neurological worsening following D-penicillamine therapy were managed with zinc monotherapy. Four patients were managed with a combination therapy of zinc and trientine. Five patients were treated with trientine monotherapy. Re-challenging with D-penicillamine at a lower dose followed by a slow dose escalation was attempted in three patients. Gradual clinical and functional status improvement was observed in 24 cases while one patient succumbed to pneumonia.
CONCLUSION
Children and adolescents with WD who had neurological worsening on D-penicillamine therapy may be managed with trientine. Zinc monotherapy with copper restricted diet was also found to be effective in non-affordable patients.
PubMed: 36211139
DOI: 10.4103/aian.aian_519_21 -
Frontiers in Immunology 2023The presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the...
BACKGROUND
The presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non-criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations.
METHODS
From a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits.
RESULTS
The addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aβ2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391).
CONCLUSION
Additional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations.
Topics: Female; Humans; Pregnancy; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; East Asian People; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lupus Erythematosus, Systemic; Penicillamine; Prevalence
PubMed: 37122726
DOI: 10.3389/fimmu.2023.1107510