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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 -
European Review For Medical and... Nov 2017Dry mouth (xerostomia), is a fairly common, well-researched condition, which is an indirect cause of oral malodour. This systematic literature review looked into another... (Review)
Review
Dry mouth (xerostomia), is a fairly common, well-researched condition, which is an indirect cause of oral malodour. This systematic literature review looked into another cause of bad breath: adverse drug reactions in the orofacial region causing halitosis. The study focused on extraoral halitosis, and its subdivisions, particularly blood borne halitosis in which malodourous compounds in the blood stream are carried to the lungs, passively diffused across the pulmonary alveolar membrane to enter the breath. An electronic search was conducted in various databases. Inclusion criteria were: editorials, case control studies, retrospective studies and randomized double-blind studies published in English between 1983 and March 2017. The search identified a total of 23 articles. According to these, drug-related halitosis may be caused by nine medications. Dimethyl sulfoxide, cysteamine and suplatast tosilate are metabolised to dimethyl sulfide, a malodourous compound that is stable in blood and is transported into the breath. Disulfiram is reduced to carbon disulfide, also a stable compound in blood. Nitric oxide reacts with foul-smelling volatile organosulfur compounds. The degradation of penicillamine raises the pH level, favouring the growth of gram-negative bacteria in the oral cavity producing halitosis. Chloral hydrate, phenothiazine, and paraldehyde could not be related to halitosis. The analysis showed that halitosis can be caused by medication but does not correlate to any specific disease or specific form of drug therapy. The pharmacological compounds identified as causes of halitosis are administered to treat a broad spectrum of diseases, or in therapeutic regimes.
Topics: Gram-Negative Bacteria; Halitosis; Humans; Hydrogen Sulfide; Penicillamine; Smell; Sulfhydryl Compounds; Sulfides
PubMed: 29164566
DOI: No ID Found -
Journal of Veterinary Internal Medicine 2013D-Penicillamine is the most commonly used copper-chelating agent in the treatment of copper-associated hepatitis in dogs. Response to therapy can be variable, and there...
BACKGROUND
D-Penicillamine is the most commonly used copper-chelating agent in the treatment of copper-associated hepatitis in dogs. Response to therapy can be variable, and there is a lack of pharmacokinetic information available for dogs. Coadministering the drug with food to alleviate vomiting has been recommended for dogs, which contradicts recommendations for drug administration to humans.
HYPOTHESIS
Coadministration of d-penicillamine with food decreases relative bioavailability and maximum plasma drug concentrations (C(max)) in dogs.
ANIMALS
Nine purpose-bred dogs with a median body weight of 17.0 kg.
METHODS
Dogs received D-penicillamine (12.5 mg/kg PO) fasted and with food in a randomized, crossover design. Blood samples were collected before and 0.25, 0.5, 1, 2, 3, 4, 8, 12, and 24 hours after dosing. Total d-penicillamine concentrations were measured using liquid chromatography coupled with tandem quadrupole mass spectrometry. Pharmacokinetic parameters were calculated for each dog.
RESULTS
Two fasted dogs (22%) vomited after receiving d-penicillamine. Mean C(max) ± standard deviation (SD) was 8.7 ± 3.1 μg/mL (fasted) and 1.9 ± 1.6 μg/mL (fed). Mean area under the plasma concentration curve ± SD was 16.9 ± 5.9 μg/mL·h (fasted) and 4.9 ± 3.4 μg/mL·h (fed). There were significant reductions in relative bioavailability and C(max) in fed dogs (P < .001).
CONCLUSIONS AND CLINICAL IMPORTANCE
Coadministration of d-penicillamine with food significantly decreases plasma drug concentrations in dogs. Decreased drug exposure could result in decreased copper chelation efficacy, prolonged therapy, additional cost, and greater disease morbidity. Administration of d-penicillamine with food cannot be categorically recommended without additional studies.
Topics: Animals; Area Under Curve; Chelating Agents; Dogs; Female; Food Deprivation; Half-Life; Male; Penicillamine
PubMed: 23875792
DOI: 10.1111/jvim.12147 -
British Medical Journal (Clinical... Mar 1981
Topics: Drug Administration Schedule; Humans; Kidney Diseases; Penicillamine; Proteinuria
PubMed: 6783160
DOI: No ID Found -
British Medical Journal Dec 1976
Topics: Adult; Arthritis, Rheumatoid; Humans; Penicillamine; Pulmonary Fibrosis
PubMed: 1000275
DOI: 10.1136/bmj.2.6050.1507-c -
The Cochrane Database of Systematic... Sep 2013The rate of retinopathy of prematurity (ROP) in moderately premature infants has decreased dramatically with improved care in the neonatal intensive care unit. A low... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The rate of retinopathy of prematurity (ROP) in moderately premature infants has decreased dramatically with improved care in the neonatal intensive care unit. A low rate of this disorder was unexpectedly observed among infants treated with intravenous D-penicillamine to prevent hyperbilirubinaemia. This observation led to the investigation of its use, both enterally as well as intravenously, to prevent ROP.
OBJECTIVES
To determine the effect of prophylactic administration of D-penicillamine on the incidence of acute ROP or severe ROP and other morbidities in preterm infants.
SEARCH METHODS
We used the Cochrane Neonatal Review Group search strategy. Two review authors independently searched multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. We updated the search on November 27, 2012.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials if they administered D-penicillamine and compared it with no treatment or placebo to premature infants and reported on the outcome of ROP.
DATA COLLECTION AND ANALYSIS
We used the criteria and standard methods of the Cochrane Neonatal Review Group to assess the methodological quality of the included trials. One review author examined trials for validity. A second review author checked validity and they reached consensus on the final data before entry into this review. We used the standards of the Neonatal Cochrane Review Group to analyse data.
MAIN RESULTS
Three randomised trials met the inclusion criteria. The meta-analysis showed no significant differences in the risk of any stage ROP (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.03 to 3.70), severe ROP (typical RR 0.38, 95% CI 0.03 to 4.26) or death (typical RR 0.95, 95% CI 0.68 to 1.32) in all treated infants. When the subgroup of infants under 1500 g birth weight was examined, the results were similar. No side effects were reported, and follow-up at one year revealed no significant differences in spasticity or developmental delay.
AUTHORS' CONCLUSIONS
Administration of prophylactic D-penicillamine in preterm infants does not prevent acute or severe ROP, death or neurodevelopmental delay. D-penicillamine cannot be recommended for the prevention of ROP based on the available evidence.
Topics: Chelating Agents; Humans; Infant, Newborn; Infant, Premature; Penicillamine; Randomized Controlled Trials as Topic; Retinopathy of Prematurity
PubMed: 24002688
DOI: 10.1002/14651858.CD001073.pub2 -
British Medical Journal Nov 1964
Topics: Cystinuria; Humans; Metabolism; Penicillamine; Toxicology; Vitamin B 6 Deficiency
PubMed: 14208217
DOI: 10.1136/bmj.2.5421.1395 -
Annals of the Rheumatic Diseases Jun 1979Information has been collected on 10 patients, 9 with marrow depression and 1 in whom the diagnosis was presumed. Six of the 10 patients died. The sequentially recorded...
Information has been collected on 10 patients, 9 with marrow depression and 1 in whom the diagnosis was presumed. Six of the 10 patients died. The sequentially recorded blood counts on at least 5 of the patients showed a downward trend of the white cell and platelet counts while D-penicillamine was still being administered. One patient suddenly developed leucopenia and thrombocytopenia with a streptococcal septicaemia.
Topics: Adult; Aged; Arthritis, Rheumatoid; Blood Cell Count; Bone Marrow Diseases; Female; Humans; Male; Middle Aged; Penicillamine; Time Factors
PubMed: 485580
DOI: 10.1136/ard.38.3.232 -
The Cochrane Database of Systematic... 2000To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA). (Review)
Review
OBJECTIVES
To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA).
SEARCH STRATEGY
We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline up to and including December 1998 and Embase from 1988-1998. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search.
SELECTION CRITERIA
All randomized controlled trials and controlled clinical trials comparing D-penicillamine against placebo in patients with rheumatoid arthritis.
DATA COLLECTION AND ANALYSIS
The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found.
MAIN RESULTS
Six trials were identified, with 425 patients randomized to D-penacillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0. 51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0. 87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities.
REVIEWER'S CONCLUSIONS
D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Penicillamine
PubMed: 10796440
DOI: 10.1002/14651858.CD001460 -
Oxidative Medicine and Cellular... 2016Iron and copper release participates in the myocardial injury under ischemic conditions and hence protection might be achieved by iron chelators. Data on copper...
Iron and copper release participates in the myocardial injury under ischemic conditions and hence protection might be achieved by iron chelators. Data on copper chelation are, however, sparse. The effect of the clinically used copper chelator D-penicillamine in the catecholamine model of acute myocardial injury was tested in cardiomyoblast cell line H9c2 and in Wistar Han rats. D-Penicillamine had a protective effect against catecholamine-induced injury both in vitro and in vivo. It protected H9c2 cells against the catecholamine-induced viability loss in a dose-dependent manner. In animals, both intravenous D-penicillamine doses of 11 (low) and 44 mg/kg (high) decreased the mortality caused by s.c. isoprenaline (100 mg/kg) from 36% to 14% and 22%, respectively. However, whereas the low D-penicillamine dose decreased the release of cardiac troponin T (specific marker of myocardial injury), the high dose resulted in an increase. Interestingly, the high dose led to a marked elevation in plasma vitamin C. This might be related to potentiation of oxidative stress, as suggested by additional in vitro experiments with D-penicillamine (iron reduction and the Fenton reaction). In conclusion, D-penicillamine has protective potential against catecholamine-induced cardiotoxicity; however the optimal dose selection seems to be crucial for further application.
Topics: Animals; Cardiotonic Agents; Catecholamines; Cell Line; Cell Survival; Deferoxamine; Hydrogen-Ion Concentration; Ions; Iron; Iron Chelating Agents; Male; Myocardium; Penicillamine; Rats, Wistar; Troponin T
PubMed: 26788248
DOI: 10.1155/2016/5213532