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Abdulla A, Rezvani A, Nelsen C, Sigala MI. D-Penicillamine Induced Myelotoxicity: A Unique Case. J Pharm Pract 2024:8971900241308626. [PMID: 39663583 DOI: 10.1177/08971900241308626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Abstract
Purpose: A case of D-penicillamine-related myelotoxicity in a patient with Wilson's disease is reported. Summary: There is a paucity of literature regarding D-penicillamine (DPA) induced myelotoxicity in the setting of Wilson's disease (WD). A 22-year-old male presented with a 1-week history of bleeding gums and dizziness. Four months prior, he had been diagnosed with Wilson's disease and started on a regimen of DPA. His blood counts demonstrated profound pancytopenia. Due to concern for suspected drug-induced myelotoxicity, DPA was discontinued. Parvovirus B19, Epstein-Barr virus, cytomegalovirus, and varicella zoster virus polymerase chain reaction studies were negative and there was no evidence of hematological malignancy. Bone marrow biopsy demonstrated hypocellularity and trilineage hypoplasia with corresponding aspirate flow cytometry confirming the absence of acute leukemia. The patient was started on subcutaneous granulocyte-colony stimulating factor, provided transfusion support with packed red blood cells and platelets. Despite these measures, his blood count failed to recover, and he was discharged on eltrombopag 150 mg daily with plans for outpatient transfusion support. DPA was permanently discontinued, and he was prescribed trientine 750 mg daily. Unfortunately, his myelotoxicity remained consistent, requiring regular transfusions. He is currently undergoing evaluation for bone marrow transplant. Conclusion: DPA-induced myelotoxicity is a rare clinical entity. Our case demonstrates a unique clinical presentation of this phenomenon. Guidelines to mitigate the risk of and treat this toxicity remain to be determined.
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Affiliation(s)
- Aliya Abdulla
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA
| | - Aryan Rezvani
- School of Medicine, Texas A&M Health Science Center, Bryan, TX, USA
| | | | - Mariah I Sigala
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA
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Mbala J, Belmalih A, Guillaud O, Lachaux A, Couchonnal Bedoya E. Evaluation of vitamin B 6 supplementation in Wilson's disease patients treated with D-penicillamine. BMJ Open Gastroenterol 2023; 10:e001211. [PMID: 37652551 PMCID: PMC10476132 DOI: 10.1136/bmjgast-2023-001211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 08/15/2023] [Indexed: 09/02/2023] Open
Abstract
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 B6; therefore, vitamin supplementation is sometimes recommended, although non-consensually. The objective of our study was to evaluate the level of vitamin B6 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 B6 supplementation. The level of vitamin B6 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 B6 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 B6 supplementation.
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Affiliation(s)
- Justin Mbala
- Department of Pediatric, Kinshasa University Hospital, Kinshasa, Congo
| | - Abdelouahed Belmalih
- Centre National de Référence Pour la Maladie de Wilson, Hospices Civils de Lyon, Lyon, France
| | - Olivier Guillaud
- Centre National de Référence Pour la Maladie de Wilson, Hospices Civils de Lyon, Lyon, France
- Ramsay Générale de Santé, Clinique de la Sauvegarde, Lyon, France
| | - Alain Lachaux
- Centre National de Référence Pour la Maladie de Wilson, Hospices Civils de Lyon, Lyon, France
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Lynch EN, Campani C, Innocenti T, Dragoni G, Forte P, Galli A. Practical insights into chronic management of hepatic Wilson’s disease. World J Clin Cases 2022; 10:4334-4347. [PMID: 35663095 PMCID: PMC9125272 DOI: 10.12998/wjcc.v10.i14.4334] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/07/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Paolo Forte
- Division of Gastroenterology, University Hospital “Careggi”, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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The epidemiology, impact, and diagnosis of micronutrient nutritional dermatoses. Part 2: B-complex vitamins. J Am Acad Dermatol 2022; 86:281-292. [DOI: 10.1016/j.jaad.2021.06.900] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/20/2021] [Accepted: 06/08/2021] [Indexed: 12/15/2022]
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Wang H, Heger M, Al-Jabiri MH, Xu Y. Vibrational Spectroscopy of Homo- and Heterochiral Amino Acid Dimers: Conformational Landscapes. Molecules 2021; 27:38. [PMID: 35011269 PMCID: PMC8746356 DOI: 10.3390/molecules27010038] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 12/15/2021] [Accepted: 12/19/2021] [Indexed: 12/19/2022] Open
Abstract
The homo- and heterochiral protonated dimers of asparagine with serine and with valine were investigated using infrared multiple-photon dissociation (IRMPD) spectroscopy. Extensive quantum-chemical calculations were used in a three-tiered strategy to screen the conformational spaces of all four dimer species. The resulting binary structures were further grouped into five different types based on their intermolecular binding topologies and subunit configurations. For each dimer species, there are eight to fourteen final conformational geometries within a 10 kJ mol-1 window of the global minimum structure for each species. The comparison between the experimental IRMPD spectra and the simulated harmonic IR features allowed us to clearly identify the types of structures responsible for the observation. The monomeric subunits of the observed homo- and heterochiral dimers are compared to the corresponding protonated/neutral amino acid monomers observed experimentally in previous IRMDP/rotational spectroscopic studies. Possible chirality and kinetic influences on the experimental IRMPD spectra are discussed.
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Affiliation(s)
| | | | | | - Yunjie Xu
- Department of Chemistry, University of Alberta, Edmonton, Alberta, AB T6G 2G2, Canada; (H.W.); (M.H.); (M.H.A.-J.)
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Gampe C, Verma VA. Curse or Cure? A Perspective on the Developability of Aldehydes as Active Pharmaceutical Ingredients. J Med Chem 2020; 63:14357-14381. [DOI: 10.1021/acs.jmedchem.0c01177] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Christian Gampe
- Genentech, 1 DNA Way, South San Francisco, 94080 California, United States
| | - Vishal A. Verma
- Genentech, 1 DNA Way, South San Francisco, 94080 California, United States
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Fux A, Pfanzelt M, Kirsch VC, Hoegl A, Sieber SA. Customizing Functionalized Cofactor Mimics to Study the Human Pyridoxal 5'-Phosphate-Binding Proteome. Cell Chem Biol 2019; 26:1461-1468.e7. [PMID: 31447350 PMCID: PMC6876276 DOI: 10.1016/j.chembiol.2019.08.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 07/09/2019] [Accepted: 08/06/2019] [Indexed: 01/29/2023]
Abstract
Pyridoxal 5′-phosphate (PLP) is a versatile cofactor that catalyzes a plethora of chemical transformations within a cell. Although many human PLP-dependent enzymes (PLP-DEs) with crucial physiological and pathological roles are known, a global method enabling their cellular profiling is lacking. Here, we demonstrate the utility of a cofactor probe for the identification of human PLP-binding proteins in living cells. Striking selectivity of human pyridoxal kinase led to a customized labeling strategy covering a large fraction of known PLP-binding proteins across various cancer-derived cell lines. Labeling intensities of some PLP-DEs varied depending on the cell type while the overall protein expression levels of these proteins remained constant. In addition, we applied the methodology for in situ screening of PLP-antagonists and unraveled known binders as well as unknown off-targets. Taken together, our proteome-wide method to study PLP-DEs in human cancer-derived cells enables global understanding of the interactome of this important cofactor.
Enrichment of human vitamin B6-binding proteins with cofactor-derived probes In situ target screening of vitamin B6 antagonists Comparison of human cell lines suggests cell-type-dependent cofactor loading states
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Affiliation(s)
- Anja Fux
- Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany
| | - Martin Pfanzelt
- Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany
| | - Volker C Kirsch
- Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany
| | - Annabelle Hoegl
- Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany
| | - Stephan A Sieber
- Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany.
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Spatial structure, thermodynamics and kinetics of formation of hydrazones derived from pyridoxal 5′-phosphate and 2-furoic, thiophene-2-carboxylic hydrazides in solution. J Mol Liq 2019. [DOI: 10.1016/j.molliq.2019.03.125] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Erriu M, Pili FMG, Cadoni S, Garau V. Diagnosis of Lingual Atrophic Conditions: Associations with Local and Systemic Factors. A Descriptive Review. Open Dent J 2016; 10:619-635. [PMID: 27990187 PMCID: PMC5123136 DOI: 10.2174/1874210601610010619] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Revised: 10/09/2016] [Accepted: 10/15/2016] [Indexed: 12/16/2022] Open
Abstract
Atrophic glossitis is a condition characterised by absence of filiform or fungiform papillae on the dorsal surface of the tongue. Consequently, the ordinary texture and appearance of the dorsal tongue, determined by papillary protrusion, turns into a soft and smooth aspect. Throughout the years, many factors, both local and systemic, have been associated with atrophic glossitis as the tongue is currently considered to be a mirror of general health. Moreover, various tongue conditions were wrongly diagnosed as atrophic glossitis. Oral involvement can conceal underlying systemic conditions and, in this perspective, the role of clinicians is fundamental. Early recognition of oral signs and symptoms, through a careful examination of oral anatomical structures, plays a crucial role in providing patients with a better prognosis.
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Affiliation(s)
- M Erriu
- Department of Surgical Sciences, Cagliari University, Cagliari, Italy
| | - F M G Pili
- Department of Surgical Sciences, Cagliari University, Cagliari, Italy
| | - S Cadoni
- Digestive Endoscopy Unit, S. Barbara Hospital, Iglesias (CA), Italy
| | - V Garau
- Department of Surgical Sciences, Cagliari University, Cagliari, Italy
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Claes DJ, Jackson E. Cystinuria: mechanisms and management. Pediatr Nephrol 2012; 27:2031-2038. [PMID: 22281707 DOI: 10.1007/s00467-011-2092-6] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2011] [Revised: 11/18/2011] [Accepted: 11/29/2011] [Indexed: 11/24/2022]
Abstract
Cystinuria is a relatively uncommon cause of pediatric stone disease, but has significant morbidity if not properly controlled because of its significant stone recurrence rate. Cystinuria is caused by the inability of the renal tubules to reabsorb filtered cystine, which is poorly soluble at a typical urine pH <7. Although many advances have been made in the understanding of the genetic and physiological basis of cystinuria, the cornerstones of treatment still involve stone prevention with dietary measures and pharmacological therapy, coupled with surgical interventions for stone removal. Pharmacological treatments can carry significant side effects that must be monitored and can limit therapy as well as impede compliance. Most patients will require surgical intervention for stone removal, although compliance with prevention strategies reduces the need for intervention.
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Affiliation(s)
- Donna J Claes
- Division of Pediatric Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, USA.
| | - Elizabeth Jackson
- Division of Pediatric Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, USA
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Side-effects of penicillamine: some recent aspects. ACTA ACUST UNITED AC 1987. [DOI: 10.1007/978-94-010-9775-8_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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Swanson BN, Ferguson RK, Raskin NH, Wolf BA. Peripheral neuropathy after concomitant administration of dimethyl sulfoxide and sulindac. ARTHRITIS AND RHEUMATISM 1983; 26:791-3. [PMID: 6305373 DOI: 10.1002/art.1780260614] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Ebadi M, Gessert CF, Al-Sayegh A. Drug-pyridoxal phosphate interactions. QUARTERLY REVIEWS ON DRUG METABOLISM AND DRUG INTERACTIONS 1982; 4:289-331. [PMID: 6087425 DOI: 10.1515/dmdi.1982.4.4.289] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
In this review it has been pointed out that vitamin B6 and its vitamers can be involved in many interactions with a number of drugs, as well as with the actions of various endocrines and neurotransmitters. Nutritional deficiencies, especially of vitamins and proteins, can affect the manner in which drugs undergo biotransformation, and thereby may also modify the therapeutic efficacy of certain drugs. The differences between nutritional vitamin B6 deficiency and the hereditary disorder producing pyridoxine dependency are discussed. In addition to a pyridoxine deficiency being able to adversely affect drug actions, the improper supplementation with vitamin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridoxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions among pyridoxine vitamers, both phosphorylated and non-phosphorylated, are briefly discussed, particularly regarding their pharmacokinetic properties. The ways in which the normal biochemical functions of vitamin B6 may be interfered with by various drugs are reviewed. (1) The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pyridoxine hydrochloride will prevent or stop these seizures. (2) The acute ingestion of excessive monosodium glutamate will, in some individuals, cause a group of symptoms including among others headache, weakness, stiffness, and heartburn, collectively known as the 'Chinese Restaurant Syndrome.' These symptoms can be prevented by prior supplementation with vitamin B6. The beneficial effect is ascribed to the correction of a deficiency in the activity of glutamic oxaloacetic transaminase, an enzyme that is dependent on pyridoxal phosphate. Some interesting relationships are pointed out between vitamin B6, picolinic acid, and zinc. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate; therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phosphate, on the other hand, appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase.(ABSTRACT TRUNCATED AT 400 WORDS)
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