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JFMS Open Reports 2023A 2-year-old spayed female domestic longhair cat was presented for evaluation of chronic ocular discharge and occasional vomiting. While physical examination findings...
CASE SUMMARY
A 2-year-old spayed female domestic longhair cat was presented for evaluation of chronic ocular discharge and occasional vomiting. While physical examination findings were consistent with an upper respiratory infection (URI), serum chemistry results revealed increased liver enzyme activities. Histopathologic examination of a liver biopsy identified substantial centrilobular accumulation of copper in hepatocytes - strongly suggestive of primary copper hepatopathy (PCH). Retrospective cytologic examination of a liver aspirate also identified copper aggregates in hepatocytes. After transitioning to a low-copper diet, 1 year of chelation therapy with D-penicillamine achieved normalization of liver enzyme activities and resolution of persistent ocular signs. Subsequently, a long-term regimen of zinc gluconate has been successfully managing the cat's PCH for almost 3 years. Sanger sequencing of the cat's gene, which encodes a copper-transporting protein, revealed a novel, 'likely pathogenic', single nucleotide variation (c.3670t/a [p.Trp1224Arg]), for which the cat is heterozygous.
RELEVANCE AND NOVEL INFORMATION
Recommendations are described for the long-term clinical management of feline PCH - a previously attainable but unreported outcome - with considerations for mitigating the speculated oxidation-exacerbated ocular risks of concurrent URI. This report is the first to include identification of copper aggregates in a liver aspirate from a cat - evidence that liver aspirates from cats could be routinely examined for copper as is standard practice for those from dogs. The cat is also the first reported with PCH and a 'likely pathogenic' heterozygous genotype, which suggests that normal alleles could be recessive to or incompletely/co- dominant with deleterious alleles in cats, as has been reported in other species.
PubMed: 37427085
DOI: 10.1177/20551169231177275 -
Tremor and Other Hyperkinetic Movements... 2024The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications.
BACKGROUND
The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications.
PHENOMENOLOGY SHOWN
This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment.
EDUCATIONAL VALUE
This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings.
HIGHLIGHTS
This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.
Topics: Humans; Copper; Hepatolenticular Degeneration; Magnetic Resonance Imaging; Penicillamine; Tremor
PubMed: 38464913
DOI: 10.5334/tohm.857 -
Micromachines Jan 2024D-penicillamine (D-PA) is a sulfur-containing drug that has been used for various health conditions. However, like any medication, overdosing on D-PA can have adverse...
D-penicillamine (D-PA) is a sulfur-containing drug that has been used for various health conditions. However, like any medication, overdosing on D-PA can have adverse effects and may require additional treatment. Therefore, developing simple and sensitive methods for sensing D-PA can play a crucial role in improving its efficacy and reducing its side effects. Sensing technologies, such as electrochemical sensors, can enable accurate and real-time measurement of D-PA concentrations. In this work, we developed a novel electrochemical sensor for detecting D-PA by modifying a carbon paste electrode (CPE) with a multi-walled carbon nanotube-CoO nanocomposite, benzoyl-ferrocene (BF), and ionic liquid (IL) (MWCNT-CoO/BF/ILCPE). Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry (CHA) were employed to explore the electrochemical response of D-PA on the developed sensor, the results of which verified a commendable electrochemical performance towards D-PA. Under optimized conditions, the developed sensor demonstrated a rapid response to D-PA with a linear dynamic range of 0.05 μM-100.0 μM, a low detection limit of 0.015 μM, and a considerable sensitivity of 0.179 μA μM. Also, the repeatability, stability, and reproducibility of the MWCNT-CoO/BF/ILCPE sensor were studied and showed good characteristics. In addition, the detection of D-PA in pharmaceutical and biological matrices yielded satisfactory recoveries and relative standard deviation (RSD) values.
PubMed: 38398949
DOI: 10.3390/mi15020220 -
JPMA. the Journal of the Pakistan... Jan 2024Wilson's disease is arare inherited disorder of copper met abolism. If le f t untre ated, i t can turn into a multi systemic disease with copper deposition in the liver,...
Wilson's disease is arare inherited disorder of copper met abolism. If le f t untre ated, i t can turn into a multi systemic disease with copper deposition in the liver, brain, a nd other tissues. Diagnosi s of Wilson's is delayed in Pak ist an by many ye a rs on average due to va riabl e presen tations. In ad olescents, the initial s igns a re more likely to b e neuropsychiatric. Here we present a case of Wilso n's disease that pre sented initially with he patic symptoms and did not have signs specific to the di sea s e such as Kayser-Fleischer rings. Our case was diagnosed to be Wilson's Disease on ly on further investigat ions and s ubsequently the patient was treated with chela tion therapy using D-Penicillamine.Wilson's Disease should be kept in mind as a differential diagno sis in adolesce nt patients that present with unexplained acute liver failure and cytopenias without any neurological symptoms, as a missed diagnosis can prove to be fatal.
Topics: Male; Humans; Hepatolenticular Degeneration; Copper; Penicillamine; Brain
PubMed: 38219193
DOI: 10.47391/JPMA.9637 -
BioMed Research International 2024[This retracts the article DOI: 10.1155/2022/3619308.].
[This retracts the article DOI: 10.1155/2022/3619308.].
PubMed: 38230034
DOI: 10.1155/2024/9810690 -
Journal of Clinical Medicine Jul 2023The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course...
BACKGROUND
The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different.
METHODS
Eighteen patients with neurological WD from a single specialized center who had been listed for liver transplantation during the last ten years and two newly diagnosed homozygous twins were recruited for this retrospective study. The mean duration of conventional treatment was 7.3 years (range: 0.25 to 36.2 years). A custom Wilson disease score with seven motor items, three non-motor items, and 33 biochemical parameters of the blood and urine, as well as the MELD score, was determined at various checkup visits during treatment. These data were extracted from the charts of the patients.
RESULTS
Treatment was initiated with severity-dependent doses (≥900 mg) of D-penicillamine (DPA) or triethylene-tetramin-dihydrochloride (TRIEN). The motor score improved in 10 and remained constant in 8 patients. Worsening of neurological symptoms was observed only in two patients who developed comorbidities (myasthenia gravis or hemispheric stroke). The neurological symptoms continuously improved over the years until the majority of patients became only mildly affected. In contrast to this slow recovery of the neurological symptoms, the MELD score and liver enzymes had already started to improve after 1 month and rapidly improved over the next 6 months in 19 patients. The cholinesterase levels continued to increase significantly ( < 0.0074) even further. One patient whose MELD score indicated further progression of liver disease received an orthotopic liver transplantation 3 months after the diagnosis of WD and the onset of DPA treatment.
CONCLUSIONS
Neurological and hepatic symptoms both respond to copper chelation therapy. For patients with acute liver failure, the first 4 months are critical. This is the time span in which patients have to wait either for a donor organ or until significant improvement has occurred under conventional therapy. For patients with severe neurological symptoms, it is important that they are treated with fairly high doses over several years.
PubMed: 37510976
DOI: 10.3390/jcm12144861 -
Journal of Clinical Medicine May 2024: Crystallization experiments of renal-calculi-forming compounds (calcium oxalate, calcium phosphates, uric acid) are normally performed by monitoring these processes...
: Crystallization experiments of renal-calculi-forming compounds (calcium oxalate, calcium phosphates, uric acid) are normally performed by monitoring these processes during periods of time similar to the residence of urine inside the kidney. Nevertheless, cystine requires high supersaturation for its crystallization, and most experiments last for longer periods. It must be considered that at high supersaturation, the inhibitors of crystalline development have poor effects. : The induction time of crystallization (t) of cystine in experimental conditions similar to those of the formation of cystine renal calculi and the effect of different cystine-binding thiol agents was determined through turbidimetric measurements. We also studied the macro- and microstructure of 30 cystine kidney stones through stereoscopic microscopy and scanning electron microscopy. : Under the studied conditions, the t in absence of crystallization inhibitors was 15 min, and the presence of 9 mM of penicillamine, tiopronin, or N-acetylcysteine totally inhibited crystallization, as their effects relate to the formation of complexes with cystine, although N-acetylcysteine also delayed cystine crystalline development and modified cystine crystal morphology. Cystine stones have traditionally been classified as smooth and rough. The study of their structure shows that all of them begin their formation from a few crystals that generate a compact radial structure. Their subsequent growth, depending on the renal cavity where they are located, gives rise to the rough structure in the form of large blocks of cystine crystals or the smooth structure with small crystals. : To prevent the development of cystine renal stones, the formation of small crystals must be avoided by reducing urinary cystine supersaturation, with N-acetylcysteine being the most effective among the studied cystine-binding thiol agents. Also, the removal of cystine crystals through increased water intake and physical activity can be a very important preventive measure.
PubMed: 38792383
DOI: 10.3390/jcm13102837 -
CEN Case Reports Apr 2024A 11-year-old girl was referred to the pediatric nephrology services of our hospital for evaluation of vitamin-D-refractory rickets. She was born to second-degree...
A 11-year-old girl was referred to the pediatric nephrology services of our hospital for evaluation of vitamin-D-refractory rickets. She was born to second-degree consanguineous parents. On examination, she had wrist widening and bilateral genu varum. She had normal anion gap metabolic acidosis, hypokalemia, and hyperchloremia. The fractional excretion of bicarbonate was 3% and the urine anion gap was positive. She also had hypercalciuria, but no phosphaturia, glucosuria or aminoaciduria. In view of a family history of an elder sister having rigidity with cognitive and speech impairment, an ophthalmic evaluation by slit lamp examination was performed in the index case that revealed bilateral Kayser-Fleischer rings. Serum ceruloplasmin was low and 24-h urine copper was elevated in the index case. Whole exome sequencing unveiled a novel pathogenic variant in exon 2 of the ATP7B gene (chr13: c.470del; Depth: 142x) (homozygous) that resulted in a frameshift and premature truncation of the protein, 15 amino acids downstream to codon 157 (p. Cys157LeufsTer15; NM_000053.4) confirming Wilson disease. There were no mutations in the ATP6V0A4, ATP6V1B1, SLC4A1, FOXI1, WDR72 genes or other genes that are known to cause distal RTA. Therapy with D-penicillamine and zinc supplements was initiated. A low dose of 2.5 mEq/kg/day of potassium citrate supplementation normalized the serum bicarbonate levels. This case was notable for the absence of hepatic or neurological involvement at admission. Wilson disease is well known to cause proximal renal tubular acidosis and Fanconi syndrome, with relatively lesser involvement of the distal renal tubules in the literature. However, isolated distal renal tubular involvement as presenting manifestation of Wilson disease (without hepatic or neurological involvement) is rare and can lead to diagnostic confusion.
Topics: Aged; Child; Female; Humans; Acidosis, Renal Tubular; Bicarbonates; Forkhead Transcription Factors; Hepatolenticular Degeneration; Mutation; Potassium Citrate; Vacuolar Proton-Translocating ATPases
PubMed: 37415038
DOI: 10.1007/s13730-023-00806-6 -
PloS One 2024Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether...
Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia.
Topics: Animals; Nanofibers; Male; Nitric Oxide; Ischemia; Cyclic GMP-Dependent Protein Kinases; Mice; Hindlimb; Mice, Inbred C57BL; Neovascularization, Physiologic; Matrix Metalloproteinase 9; Phosphoproteins; Microfilament Proteins; Cell Adhesion Molecules
PubMed: 38768136
DOI: 10.1371/journal.pone.0303758 -
Internal Medicine (Tokyo, Japan) Apr 2024No reports of renal cancer in patients with Wilson's disease (WD) exist. We herein report a 37-year-old Japanese man diagnosed with WD who had been treated with...
No reports of renal cancer in patients with Wilson's disease (WD) exist. We herein report a 37-year-old Japanese man diagnosed with WD who had been treated with d-penicillamine 9 years prior. Hepatocellular carcinoma had been diagnosed at 36 years old and treated with radiofrequency ablation therapy. One year later, renal cancer and recurrent hepatocellular carcinoma had developed. The hepatocellular carcinoma was treated after renal cancer surgical resection of a clear-cell-type renal cell carcinoma, with iron, rather than copper, deposited on the renal cancer cells. This patient harbored a novel mutation, p. Leu1395Terfs in ATP7B.
Topics: Male; Humans; Adult; Carcinoma, Hepatocellular; Hepatolenticular Degeneration; Carcinoma, Renal Cell; Liver Neoplasms; Copper; Kidney Neoplasms
PubMed: 37612087
DOI: 10.2169/internalmedicine.2056-23