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Current Urology Reports Aug 2023We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and... (Review)
Review
PURPOSE OF REVIEW
We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and complication rates, based on all the available literature evidence.
RECENT FINDINGS
A systematic review of literature was performed for all studies with paediatric cystine stone management. Twelve studies met the eligibility criteria, of which 4 analysed outcomes of SWL, 2 of URS and 3 of PCNL and 3 focused on the effect of either alkalising agents (potassium citrate, citric acid) or cysteine-binding thiol (CBT) agents (tiopronin, penicillamine). The reported SFR in studies ranged from 50 to 83%, 59 to 100% and 63 to 80.6%, with a complication rate of 2.8-51%, 14-27% and 12.9-15.4% with SWL, URS and PCNL, respectively. Paediatric cystine stones treatment should aim at complete stone clearance, preservation of renal function and prevention of further recurrences. SWL achieves inferior results in case of cystine stones. URS and PCNL are safe and effective procedures in the paediatric population, with a low rate of major complications. Adherence to medical prevention therapies may prolong recurrence-free periods.
Topics: Humans; Child; Kidney Calculi; Cystine; Lithotripsy; Ureteroscopy; Ureteral Calculi; Treatment Outcome
PubMed: 37079195
DOI: 10.1007/s11934-023-01162-9 -
The Canadian Veterinary Journal = La... Jul 2023Copper-associated hepatitis in dogs results from elevated copper levels secondary to increased intake or decreased clearance. Treatment is through establishing a...
Copper-associated hepatitis in dogs results from elevated copper levels secondary to increased intake or decreased clearance. Treatment is through establishing a negative copper balance and can include chelation therapy. Traditionally, chelation therapy in dogs is uses D-penicillamine, which has been shown to have severe side effects in humans. Side effects have not been well-documented in dogs but can include nephrotoxicity and dermatologic reactions. This article is the first to report neutropenia in a dog secondary to chelation therapy using D-penicillamine. In this case, a complete blood (cell) count (CBC) collected before initiation of chelation therapy was normal and neutropenia was documented 4 mo after starting therapy. A cytologic examination of bone marrow confirmed a myeloid hypoplasia. Following discontinuation of D-penicillamine, the neutropenia resolved. Based on this case report, periodic CBC rechecks following the initiation of D-penicillamine chelation therapy are recommended to guide treatment decisions. Key clinical message: Dogs with confirmed copper-associated hepatitis should be treated cautiously with D-penicillamine for chelation therapy. D-penicillamine may adversely affect bone marrow, causing a leukopenia characterized by neutropenia. It is recommended that clinicians periodically monitor neutrophil counts while treating dogs with D-penicillamine.
Topics: Humans; Dogs; Animals; Penicillamine; Copper; Chelating Agents; Neutropenia; Dog Diseases
PubMed: 37397696
DOI: No ID Found -
Carbohydrate Polymers Aug 2022Chiral recognition is of significant importance in the fields of chemical asymmetric synthesis and biological pharmaceutical research. In this work, an electrochemical...
Chiral recognition is of significant importance in the fields of chemical asymmetric synthesis and biological pharmaceutical research. In this work, an electrochemical chiral sensor with two kinds of chiral sites (chiral cavity for β-cyclodextrin and chiral skeleton for Ca-sacc/MeOH) by electrooxidation β-cyclodextrin onto Ca-sacc/MeOH was built. The proposed multichiral β-CD@Ca-sacc/MeOH/GCE can be used for recognition of tryptophan and penicillamine enantiomers simultaneously with wide linear range, low detection limits value, high repeatability and stability within the available electrochemical window. The strategy for integration multichiral sources is crucial to construct novel chiral platforms for simultaneous recognition of multiple chiral compounds in complicated chiral systems.
Topics: Electrochemical Techniques; Penicillamine; Stereoisomerism; Tryptophan; beta-Cyclodextrins
PubMed: 35550750
DOI: 10.1016/j.carbpol.2022.119474 -
Clinical Neurology and Neurosurgery Aug 2023A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically... (Review)
Review
BACKGROUND
A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically reviewed clinical outcomes in glioma patients treated with one or more nutritional adjunct and/or an antimetabolite drug.
METHODOLOGY
A systematic review of the literature following PRISMA guidelines was performed using Pubmed from inception till February 2023. In total, 22 manuscripts on nutrition representing 828 patients were included in the review. Statistical analyses were performed to compare the outcomes of various adjuncts.
RESULTS
The median overall survival (OS) increased for newly diagnosed (21 months) and recurrent cases (10 months) when compared to historical data. For newly diagnosed cases, a ketogenic diet had the highest median OS of all the adjuncts (42.6 months) while in recurrent cases, a low copper diet coupled with 1 g penicillamine had the highest median OS (18.5 months). However, no statistically significant difference was observed in OS or progression-free survival (PFS) of newly diagnosed or recurrent gliomas.
CONCLUSION
While nutritional adjuncts may offer a therapeutic benefit in the treatment of glioma, more human subject research is needed to derive meaningful conclusions.
Topics: Humans; Neoplasm Recurrence, Local; Glioma; Progression-Free Survival; Brain Neoplasms
PubMed: 37390567
DOI: 10.1016/j.clineuro.2023.107853 -
Annals of Translational Medicine Apr 2021Wilson disease is a copper overload disease treatable with the chelators D-penicillamine and trientine to enhance urinary excretion or with zinc which predominantly... (Review)
Review
Wilson disease is a copper overload disease treatable with the chelators D-penicillamine and trientine to enhance urinary excretion or with zinc which predominantly inhibits absorption. By lifelong treatment a normal life expectancy and significant improvement of hepatic injury as well as neurologic manifestation is achievable. Here we evaluate the mode of action for effective therapy of Wilson disease. We postulate that there is no quantitative removal of copper from the liver possible. The therapeutic goal is the removal of toxic free copper (non-ceruloplasmin, but albumin bound copper). This is achievable by the induction of metallothionein which is accomplished by chelators and in particular by zinc. For control of therapy the option of a direct measurement of free copper would be preferable over the less reliable calculation of this fraction. A therapeutic challenge is still the full restoration of neurological deficits which can hardly be reached by the available chelators. Whether bis-choline-tetrathiomolybdate as intracellular copper chelator is an option has to be awaited. It is concluded that the goal of actual drug therapy in Wilson disease is the normalization of free copper in serum.
PubMed: 33987430
DOI: 10.21037/atm-20-3090 -
World Journal of Hepatology Nov 2021Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson's disease (WD), one of the common... (Review)
Review
Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson's disease (WD), one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine. D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation. Trientine, an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects. The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD. Indian childhood cirrhosis is related to excessive copper ingestion, rarely seen in present era. D-Penicillamine is effective in the early part of this disease with reversal of clinical status. Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias. There are strict chelation protocols during bone marrow transplant. The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy. Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.
PubMed: 34904029
DOI: 10.4254/wjh.v13.i11.1552 -
Biomolecules Nov 2022The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead... (Review)
Review
The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead (Pb) in poisoned individuals. However, DMSA, PSH, EDTA (ethylenediamine tetraacetate), and deferoxamine (DFOA) are water-soluble agents with limited access to the central nervous system (CNS). Strategies for mobilization of metals such as manganese (Mn), iron (Fe), and Cu from brain deposits may require the combined use of two agents: one water-soluble agent to remove circulating metal into urine, in addition to an adjuvant shuttler to facilitate the brain-to-blood mobilization. The present review discusses the chemical basis of metal chelation and the ligand exchange of metal ions. To obtain increased excretion of Mn, Cu, and Fe, early experiences showed promising results for CaEDTA, PSH, and DFOA, respectively. Recent experiments have indicated that p-amino salicylate (PAS) plus CaEDTA may be a useful combination to remove Mn from binding sites in CNS, while the deferasirox-DFOA and the tetrathiomolybdate-DMSA combinations may be preferable to promote mobilization of Fe and Cu, respectively, from the CNS. Further research is requested to explore benefits of chelator combinations.
Topics: Humans; Manganese; Copper; Iron; Chelating Agents; Ions; Metals; Neurotoxicity Syndromes; Succimer; Water
PubMed: 36421727
DOI: 10.3390/biom12111713 -
Nanomaterials (Basel, Switzerland) Apr 2023Inorganic chiral nanoparticles are attracting more and more attention due to their peculiar optical properties and potential biological applications, such as bioimaging,...
Inorganic chiral nanoparticles are attracting more and more attention due to their peculiar optical properties and potential biological applications, such as bioimaging, therapeutics, and diagnostics. Among inorganic chiral nanoparticles, gold chiral nanostructures were demonstrated to be very interesting in this context, with good physical chemical stability and also the possibility to decorate the surface, improving biomedical application as the interaction with the bio-systems. Gold (Au) nanostructures were synthesized according to a seed-mediated procedure which envisages the use of cetyltrimethylammonium bromide (CTAB) as the capping agent and L- and D-cysteine to promote chirality. Au nanostructures have been demonstrated to have opposite circular dichroism signals depending on the amino acid enantiomer used during the synthesis. Then, a procedure to decorate the Au surface with penicillamine, a drug used for the treatment of Wilson's disease, was developed. The composite material of gold nanoparticles/penicillamine was characterized using electron microscopy, and the penicillamine functionalization was monitored by means of UV-Visible, Raman, and infrared spectroscopy, highlighting the formation of the Au-S bond. Furthermore, electron circular dichroism was used to monitor the chirality of the synthesized nanostructures and it was demonstrated that both penicillamine enantiomers can be successfully bonded with both the enantiomers of the gold nanostructures without affecting gold nanoparticles' chirality. The effective modification of nanostructures' surfaces via penicillamine introduction allowed us to address the important issue of controlling chirality and surface properties in the chiral nano-system.
PubMed: 37177071
DOI: 10.3390/nano13091526 -
Seminars in Arthritis and Rheumatism Aug 2024Drug-induced dermatomyositis (DIDM) is a rare and underestimated variant of dermatomyositis (DM) characterized by muscle damage and skin rash and related to certain drug... (Review)
Review
Drug-induced dermatomyositis (DIDM) is a rare and underestimated variant of dermatomyositis (DM) characterized by muscle damage and skin rash and related to certain drug exposure. The spectrum of drugs causing DIDM has evolved over time, originally implicating hydroxyurea, penicillamine, and statins as causative agents. Tumor necrosis factor α inhibitors and immune checkpoint inhibitors have also been associated with such conditions. To bridge the gap between current literature and clinical practice, and therefore guide clinicians, we conducted a comprehensive review of English literature from Pubmed, EMBASE, and MEDLINE. Our analysis included demographic data, clinical features, laboratory findings, therapeutic outcomes, and extant research pertaining to the probable pathogenesis of DIDM induced by various drugs. Furthermore, we categorized the drugs involved in DIDM cases into biologics and traditional agents for subsequent statistical analysis. Over time, there has been a gradual accumulation of reported DIDM cases. A total of 69 published DIDM cases were documented in our study, among which 33 should be attributed to biologics and the remaining 36 to traditional drugs. Interestingly, 41 of all DIDM cases had a previous history of malignancies. Additionally, DIDM cases exhibited similar cutaneous and muscular manifestations to classic DM, with the exception of cases induced by hydroxyurea, which did not entail muscle damage. Positive antinuclear antibodies and anti-TIF1-γ autoantibodies have been predominantly observed in biologics-induced cases, while positive anti-TIF1-γ antibodies were merely reported in the cases that were primarily diagnosed with malignant diseases and exposed to ICIs afterwards. Anti-TIF1-γ antibodies may potentially serve as a red flag in the identification of co-existing malignant diseases in DM patients. We also provided a comprehensive summary and exploration of potential mechanisms lying behind drug-induced dermatomyositis. In conclusion, our review consolidates the current literature on DIDM, highlighting the evolving spectrum of medications and elucidating the differences in clinical manifestations, laboratory findings, and underlying mechanisms.
Topics: Dermatomyositis; Humans; Biological Products
PubMed: 38833729
DOI: 10.1016/j.semarthrit.2024.152478 -
BioMed Research International 2022The purpose of this study is to investigate the exchange reaction taking place among the bovine serum albumin (BSA), 5,5'-dithiobis-(2-nitrobenzoic acid (ESSE), reduced...
The purpose of this study is to investigate the exchange reaction taking place among the bovine serum albumin (BSA), 5,5'-dithiobis-(2-nitrobenzoic acid (ESSE), reduced glutathione, N-acetylcysteine, D-penicillamine (thiolates), and silver metal (Ag). For this purpose, stock solutions of BSA and Ellman's reagent were prepared by dissolving 264 mg of BSA in 5 ml of reaction buffer (0.1 M KHPO at pH 7.8) and 23.8 mg of ESSE in 1.0 ml of reaction buffer which were mixed together. Mixture of BSA-Ag was prepared in a separate procedure by dissolving 0.17 mg of silver nitrate in 1 ml of reaction buffer and then dissolving BSA (200 mg) in the same solution of silver nitrate. Blocking of Cys-34 of BSA with Ag was confirmed by treating different dilutions of BSA-Ag (500 M) solutions with the solutions of ESSE (85 M) and ES (85 M) and recording the spectra (300-450) with a UV-visible spectrophotometer. The chromatographed Ag-modified BSA ((BSA-S)Ag)) samples (typically 500 M) were subsequently mixed with thiolates (reduced glutathione, N-acetylcysteine, and D-penicillamine). Ag and modified BSA (typically 500 M each) were treated with these low molecular weight thiolates and allowed to react overnight followed by chromatographic separation (Sephadex G25). The redox reactions of Ag-modified BSA with various low molecular weight thiols revealed a mechanically important phenomenon. In the case of reduced glutathione and N-acetylcysteine, we observed the rapid release of a commensurate amount of Ellman's anion, indicating that an exchange has taken place and low molecular weight thiols (RSH) substituted Ag species at the Cys-34 of BSA eventually forming disulfide (BSA-SSR) at Cys-34. It can be anticipated from the phase of study involving bovine serum albumin that low molecular weight thiolates (reduced glutathione and N-acetylcysteine) take off Ag which are attached to proteins elsewhere in the physiological system, making these toxic metals free for toxic action.
Topics: Acetylcysteine; Coordination Complexes; Cysteine; Glutathione; Metals; Penicillamine; Serum Albumin, Bovine; Silver Nitrate; Sulfhydryl Compounds
PubMed: 35978640
DOI: 10.1155/2022/3619308