Probing and gauging of D-Penicillamine xenobiotics in hepatic Wilson disease patients.

D-penicillamine (PA) is the primary chelator of choice to treat Wilson disease (WD). There are limitations in obtaining comprehensive data on PA metabolites in biological specimens by conventional approaches. Hence, the aim of the present was to identify the major hepatic PA metabolites and draw clear conclusions of the drug's xenobiotic in WD. Urine samples were collected from children with hepatic WD (n = 63, aged 14.8 ± 4 years) 5 h after PA administration (16.3 ± 3.8 mg/kg/day) and age-matched healthy volunteers comprised as controls (n = 30). High-resolution 800 MHz nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry was applied to reveal unambiguous appraisals of different excretory by-products of PA metabolism. Four new products comprising penicillamine disulphide (PD), penicillamine cysteine disulphide (PCD), S-methyl penicillamine (SMP), and N-acetyl penicillamine (NAP) of PA xenobiotic metabolites were identified using high-resolution NMR spectroscopy. Quantitative levels of PCD and SMP were approximately three-fold higher than those of PD and NAP, respectively. High-resolution NMR identifies the major PA metabolites with certainty. Reduction, sulfation, and methylation are the predominant pathways of PA metabolism. There is a potential application for assessing therapeutic monitoring of chelation in hepatic WD.

Efficacy and safety of D-penicillamine, trientine, and zinc in pediatric Wilson disease patients.

OBJECTIVES: Wilson disease (WD) is a rare genetic disease affecting copper metabolism and the biliary tract's copper excretion. Lifelong medication is necessary to prevent liver failure, neurological complications, and death. Although D-penicillamine (DPA), trientine, and zinc are used to treat WD, there is limited research on the long-term outcomes of these drugs, especially in children. This study aimed to evaluate the efficacy and safety of DPA, trientine, and zinc in patients diagnosed with WD during childhood. METHODS: Ninety out of 92 patients were included in the analysis, excluding two patients who underwent liver transplantation without drug treatment due to an acute liver failure diagnosis. Treatment outcomes and reasons for discontinuation of therapy in 148 treatment blocks (37 DPA, 50 trientine, and 61 zinc) were analyzed using Kaplan-Meier analysis. RESULTS: The median age at diagnosis was 8.3 years. There was a statistically significant difference in drug changes due to treatment ineffectiveness among the three drugs: trientine (22/50, 44%), zinc (15/61, 25%), and DPA (2/37, 5%) (all p < 0.05). Regarding drug changes due to adverse effects, the rate was the highest for DPA, followed by zinc and trientine. There were significant differences between DPA and zinc, zinc and trientine (all p < 0.05), but no significant difference was observed between DPA and zinc (p = 0.22). CONCLUSIONS: In pediatric WD, DPA, zinc, and trientine have therapeutic effects in that order. However, DPA and zinc are associated with more adverse effects compared to trientine.

Wilson Disease in Children in the Eastern Region of Morocco: Analysis of 24 Cases.

Wilson's disease (WD), or "hepato-lenticular degeneration," is a rare genetic disorder of autosomal recessive inheritance causing toxic tissue accumulation of copper, mainly in the liver, brain, and cornea. Its phenotypic and genotypic heterogeneity characterizes it. This study aimed to clarify the clinical features and spectrum of Wilson's disease in children from the eastern region of Morocco and to study the evolutionary profile and survival in this population while discussing and highlighting the various diagnostic and therapeutic difficulties encountered in the management of WD in our context. This retrospective study encompassed 24 children diagnosed with Wilson's disease, selected from the gastroenterology-hepatology and pediatric nutrition units at Mohamed VI University Hospital in Oujda, Morocco, over a span of nine years, from January 2015 to November 2023. Our series results show 14 boys and 10 girls; the median age of discovery was 11 years, with extremes ranging from 18 months to 15 years. The consanguinity was found in 13 patients. Clinically, the edemato-ascitic syndrome was noted in 14 patients with an alteration of the general state; icterus was found in 13 patients; signs of portal hypertension were present in six patients; and neurological signs in seven cases. Skin manifestations occurred in three cases, and arthralgia in three cases. Six children were diagnosed on the occasion of a family screening. Biologically, hepatic cytolysis was found in 20 patients, with signs of hepatocellular failure in 15 cases. Hemolytic anemia was present in nine patients. Ceruloplasminemia was decreased in 21 patients and cupremia in 19 patients. Cupruria was increased in 22 cases. The Kayser-Fleicher ring was found in 10 cases. Abdominal ultrasound showed ascites in 16 patients, hepatomegaly in 1, splenomegaly in two cases, hepatosplenomegaly in five cases, and cirrhosis in two. MRI showed signal abnormalities in 11 patients. Therapeutically, D-penicillamine was initially introduced in 18 patients and zinc acetate in 6 patients. The evolution was favorable for 15 patients still followed up in the department. Three patients died of hepatocellular failure, and two died of hepatic encephalopathy. Four patients were lost to follow-up.

Atypical Presentation of Wilson Disease: Unravelling a Clinical and Radiological Complexity in a Rare Case.

Wilson disease (WD) is an autosomal recessive disorder marked by aberrations in copper metabolism, leading to its accumulation in vital organs such as the liver, brain, cornea, kidneys, and heart. While WD typically presents with hepatic symptoms in early childhood, neuropsychiatric manifestations are more prevalent during adolescence. This case report highlights an extraordinary instance of WD in an eight-year-old girl, characterized by intricate clinical and radiological features. The patient exhibited atypical symptoms, emphasizing the importance of recognizing diverse presentations of WD. Delayed diagnosis and treatment initiation can prove fatal in WD cases, underscoring the significance of awareness regarding these unusual clinical and radiological features to facilitate prompt intervention and prevent adverse outcomes.

Construction and Application of an Electrochemical Sensor for Determination of D-Penicillamine Based on Modified Carbon Paste Electrode.

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-Co3O4 nanocomposite, benzoyl-ferrocene (BF), and ionic liquid (IL) (MWCNT-Co3O4/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-1. Also, the repeatability, stability, and reproducibility of the MWCNT-Co3O4/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.

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study / Elevada heterogeneidad en el diagnóstico y tratamiento a largo plazo en la enfermedad de Wilson: resultados de un estudio multicéntrico español

There is uncertainty regarding Wilson's disease (WD) management. Objectives: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. Methods: Data on WD patients followed at 32 Spanish hospitals were collected. Results: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. Conclusions: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored. (AU)

Existe incertidumbre con respecto al manejo de la enfermedad de Wilson (EW). Objetivos: Evaluar, en un estudio de cohorte retrospectivo español multicéntrico, si el abordaje de la EW es homogéneo entre los centros. Métodos: Se recogieron datos sobre pacientes con EW seguidos en 32 hospitales españoles. Resultados: Un total de 153 casos, 58% hombres, 20,6 años al diagnóstico, 69,1% presentación hepática, fueron seguidos durante 15,5 años. Se objetivaron resultados discordantes en parámetros de laboratorio no invasivos en el 39,8%. La concentración intrahepática de cobre fue patológica en el 82,4%. Las pruebas genéticas solo se realizaron en el 56,6% con resultados positivos en el 83,9%. Un diagnóstico definitivo de EW (puntuación de Leipzig ≥4) se confirmó retrospectivamente en el 92,5% de los casos. Los agentes quelantes fueron la terapia inicial estándar (75,2%) con modificaciones frecuentes (57%), particularmente hacia zinc de mantenimiento. La normalización enzimática no se logró en un tercio, más comúnmente en el contexto de un cumplimiento deficiente, ausencia de mutaciones genéticas y/o presencia de factores de riesgo cardiometabólicos. Aunque sin alcanzar significación estadística, observamos diferencias entre hombres y mujeres en el número de casos, edad en el momento del diagnóstico y la respuesta bioquímica. Conclusiones: De este estudio multicéntrico que incluye centros de referencia pequeños y grandes se desprende una heterogeneidad significativa en el diagnóstico y manejo de los pacientes con EW. La incorporación de pruebas genéticas ha mejorado el diagnóstico. Las diferencias de sexo deben explorarse más a fondo en estudios futuros. (AU)

Enfermedad de Wilson: presentación hepática y revisión bibliográfica / Wilson's disease: liver presentation and literature review / Doença de Wilson: apresentação hepática e revisão de literatura

Resumen: La Enfermedad de Wilson es un trastorno genético raro que puede presentarse a cualquier edad y se caracteriza por el depósito de cobre a nivel hepático y cerebral. La afectación hepática abarca desde formas asintomática hasta falla hepática fulminante o cirrosis. Su diagnóstico precoz tiene implicancias pronósticas ya que el tratamiento puede lograr un balance negativo de cobre, permitir el control sintomático y prevenir la progresión de la enfermedad. Se presenta el caso de un hombre de 27 años, con dolor abdominal, en el que se hizo el diagnóstico de Enfermedad de Wilson a partir de una hipertransaminasemia leve. Los hallazgos que orientaron al diagnóstico fueron una cupruria aumentada por inducción con D-penicilamina y una cuantificación de cobre en tejido hepático seco elevada. Con un estadio de fibrosis leve, se comenzó tratamiento con D-penicilamina con buena tolerancia y la normalización de las alteraciones bioquímicas.

Abstract: Wilson's disease is a rare genetic disorder that can occur at any age and is characterized by copper deposition in the liver and brain. Liver involvement ranges from asymptomatic forms to fulminant hepatic failure or cirrhosis. Its early diagnosis has prognostic implications since the treatment can achieve a negative copper balance, allow symptomatic control and prevent the progression of the disease. We present the case of a 27-year-old man with abdominal pain, who was diagnosed with Wilson's disease from mild hypertransaminasemia. The findings that led to the diagnosis were an increased cupruria by induction with D-penicillamine and a quantification of copper in elevated dry liver tissue. With a stage of mild fibrosis, treatment with D-penicillamine was started with good tolerance and normalization of biochemical alterations.

Resumo: Doença de Wilson é uma doença genética rara que pode ocorrer em qualquer idade e é caracterizada pela deposição de cobre no fígado e no cérebro. O envolvimento do fígado varia de formas assintomáticas a insuficiência hepática fulminante ou cirrose. Seu diagnóstico precoce tem implicações prognósticas, uma vez que o tratamento pode alcançar um balanço negativo do cobre, permitir o controle sintomático e prevenir a progressão da doença. Apresentamos o caso de um homem de 27 anos com dor abdominal, diagnosticado com doença de Wilson de hipertransaminasemia leve. Os achados que levaram ao diagnóstico foram aumento da cuprúria por indução com D-penicilamina e quantificação de cobre em tecido hepático seco elevado. Com uma fase de fibrose leve, o tratamento com D-penicilamina foi iniciado com boa tolerância e normalização das alterações bioquímicas.

D-penicillamine Induced Elastosis Perforans Serpiginosa / 대한피부과학회지

No abstract available.

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico

Las nefropatías tóxicas secundarias a la exposición ocupacional a metales han sido ampliamente estudiadas. La nefropatía membranosa por mercurio es poco frecuente.La intoxicación ocupacional con mercurio sí es frecuente, siendo las principales formas de presentación las manifestaciones clínicas neurológicas. La afectación renal secundaria a la exposición crónica a mercurio metálico puede desarrollar enfermedad glomerular por depósito de inmunocomplejos. La glomerulopatía membranosa y a cambios mínimos son las más frecuentemente comunicadas.Se presenta el caso de un paciente con exposición ocupacional a mercurio metálico, con síndrome nefrótico y biopsia renal con glomerulopatía membranosa que presentó respuesta favorable luego del tratamiento quelante e inmunosupresor.(AU)

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.(AU)

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico

Las nefropatías tóxicas secundarias a la exposición ocupacional a metales han sido ampliamente estudiadas. La nefropatía membranosa por mercurio es poco frecuente.La intoxicación ocupacional con mercurio sí es frecuente, siendo las principales formas de presentación las manifestaciones clínicas neurológicas. La afectación renal secundaria a la exposición crónica a mercurio metálico puede desarrollar enfermedad glomerular por depósito de inmunocomplejos. La glomerulopatía membranosa y a cambios mínimos son las más frecuentemente comunicadas.Se presenta el caso de un paciente con exposición ocupacional a mercurio metálico, con síndrome nefrótico y biopsia renal con glomerulopatía membranosa que presentó respuesta favorable luego del tratamiento quelante e inmunosupresor.

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

Effect of Lead Intoxication and D-Penicillamine Treatment on Hematological Indices in Rats / Efectos de Intoxicación con Plomo y Tratamiento de D-Penicilamina en índices Hematológicos en Ratas

Lead is one of the most important environmental pollution which is toxic to many organ systems. D-penicillamine (D-P) is a chelator drug which is used for treatment of lead toxicity for several years. This study was conducted in order to evaluate the efficacy of D-P in reducing the effects of lead on hematological indices. This study was done on 36 male adult, 6-8 weeks albino Wistar rats in Gorgan University of Medical Sciences. At first male adult rats were exposed to lead acetate in their drinking water. After 8 weeks, 6 rats were selected and blood samples were prepared to assess the effects of lead toxicity. The remained lead exposed rats were divided into recovery and treatment groups where distilled water and D-P was administered for them, respectively. After lead exposure, red blood cell count increased slightly, but hemoglobin and hematocrite were decreased. Also MCV and MCH were significantly decreased (P<0.05). RDW, PDW and MPV were significantly higher in lead exposed rats (P<0.05). After recovery period, most of parameters were close to normal while there were no significant differences between recovery and treatment groups. This study showed that hematologic effects of lead are reversible and D-P administration do not play an important role in subchronic lead intoxication.

El plomo es uno de los más importantes contaminantes ambientales, tóxico para la mayoría de los sistemas orgánicos. La D-penicillamina (D-P) es una droga quelante, la cual se ha usado para el tratamiento de la toxicidad por plomo durante varios años. Este estudio fue dirigido para evaluar la eficacia de la D-P en la reducción de los efectos del plomo en los índices hematológicos. Este estudio se realizó en 36 machos adultos de ratas Wistar albinas de 6-8 semanas, en la Universidad de Ciencias Médicas de Gorgan, Irán. Al inicio, las ratas machos adultas fueron expuestas al acetato de plomo en el agua de beber. Después de 8 semanas, 6 ratas se seleccionaron para evaluar los efectos de la toxicidad del plomo en muestras sanguíneas. Las restantes ratas expuestas fueron divididas para su recuperación, a las cuales se les administró agua destilada y un grupo con tratamiento al que se le suministró D-P. Después de la exposición al plomo, el conteo de glóbulos rojos se incrementó ligeramente, pero la hemoglobina y el hematocrito disminuyeron. También el MCV y el valor de MCH disminuyeron significativamente (P< 0,05). Los valores de RDW, PDW y MPV fueron significativamente altos en las ratas expuestas al plomo (p< 0,05). Luego del periodo de recuperación, la mayoría de los parámetros se acercaron al valor normal y no hubo diferencias significativas entre el grupo recuperado y con tratamiento. Este estudio mostró que los efectos hematológicos del plomo son reversibles y la administración de D-P no juega un rol importante en la intoxicación subcrónica.

A Case of Lead Poisoning After Ingestion of Herb Pills / 대한산업의학회지

BACKGROUND: Lead is a common environmental metal and has been used for various purposes for a long time, leading to frequent reports of lead poisoning. The concern about lead poisoning starts has been mostly focused on occupational exposure and is linked to the prevention and management of lead exposure in refining and manufacturing processes. Nowadays, however, there is growing concern about nonoccupational lead exposure by many pollutants. Especially, lead poisoning by herb medicine has commonly been observed in clinics in Southeast Asia and South Korea. This case report contains diagnosis of inpatients who suffered from lead poisoning from a herb medicine, arthritis remedy and who complained of abdominal symptoms and dizziness. The study purpose was to awaken our healthful interest in lead poisoning. CASE REPORT: A 53-year-old female patient complaining of abdominal pain, dizziness, and numbness of hand and foot came to our hospital due to the continuation of her anemic finding symptoms while undergoing treatment at a secondary hospital. Her past medical history was unremarkable except she had taken herb pills for about a year which were administered by herb medicine to treat arthritis. Physical examination was unremarkable except for oral ulcer finding. Hemoglobin was 8.5 g/dl, reticulocyte count was 4.10%, bilirubin was 1.3 mg/dl (direct 0.3 mg/dl), and Zinc protoporphyrin 169.12 ug/dl. In urinalysis results, WBC increased to 30~39 /HPF, While AST/ALT, BUN/Cr, PT/aPTT, and nerve conduction velocity were normal. Basophilic stippling was observed through peripheral blood smear. The blood lead level was 80.4 microgram/dl and the urine lead level continued to increase to 541 microgram/l. Analysis of the pills that the patient had been taking showed that they contained 30 mg/g lead. By oral chelation therapy with D-penicillamine four times per day for five days, the patient's hemoglobin increased to 11.8 g/dl, while blood lead level decreased to 39.2 microgram/dl, and urine level to 196 microgram/l. Although the soles of her feet remained cold, but other symptoms and anemia finding were improved considerably. However, after discontinuing D-penicillamine medication, the blood lead level increased to 41.4 microgram/dl again. The further administration of D-penicillamine for five days reduced the blood lead level to 31.5 microgram/dl. At two years after the discontinuance of D-penicillamine, the followup findings were normal; hemoglobin was 13.1 g/dl, hematocrit 39.6%, reticulocyte count 1.22%, blood lead level 13.3 microgram/dl, and urine lead level 9.17 microgram/l. CONCLUSION: After taking herb medicine pills for one year, the patient was admitted to hospital chiefly complaining of abdominal pain, dizziness, and numbness of the hand and foot. The high blood and urine and lead levels and lead chemical analysis of the herb pills confirmed lead poisoning which was treated with D-penicillamine for five days. The follow-up result after two years indicated normal blood and urine lead levels.

Acetylized Racemization Process and Kinetics of D-penicillamine / 中国药房

OBJECTIVE:To study the process of acetylized racemization of D-penicillamine in the acidic condition. METHODS:The acetylized racemic mixture of D-penicillamine was prepared by racemizing acetyl chloride in acetic acid solu_tion with D-penicillamine as feedstock.The preparation process was optimized with the quantities of solvent and acetyl chloride,the reaction temperature,the reaction time etc.as parameters.The influence of reaction temperature,reaction time on the specific optical rotation in the acetylized process was determined and the kinetic equation of acylation process was computed. RESULTS:The optimal condition for racemization was the following,the quantity ratios of D-penicillamine-acetic acid -acetyl chloride were 1∶7∶2,the reaction temperature was 80℃ and the reaction time was 5h.The kinetic equation of acylation process fitted first order linear relation. CONCLUSION:This preparation process is mild and simple,and it offers direct feedstock for the preparation of D,L-penicillamine.

Early Onset of Minimal change Nephrotic Syndrome during Treatment with D-penicillamine in a Patient with Wilson s Disease

Wilson s disease is an autosomal recessive disorder characterized by degenerative changes in the brain, liver, and cornea. Treatment includes D-penicillamine, trientine, and zinc sulfate. D-penicillamine has been used frequently as first line therapy for Wilson s disease. However, nephrotoxicity can occur after D-penicillamine treatment. Among them membranous glomerulopathy is the most common histological abnormality but minimal change lesions have also been reported. Nephrotic syndrome is a late complication of D-penicillamine treatment but very rarely can occur within 2 months after treatment of D-penicillamine. We report the early development of minimal change nephrotic syndrome in a 3-year-old girl with Wilson s disease 3 weeks after initiation of D-penicillamine.

Breast Gigantism Induced by D-Penicillamine: Case Report

D-penicillamine, a chelating agent of copper, is the drug of choice for the treatment of Wilson's disease. Breast enlargement is a rare complication arising from its use, and we report a case of breast gigantism which developed after it had been used for ten months to treat this condition. Mammography demonstrated bilaterally enlarged dense breasts; ultrasonography, similarly, demonstrated enlargement, revealing the presence of a mass, shown at biopsy to be benign, in the left one.

Subcutaneous and Gastrointestinal Exposure to Metallic Mercury: Report of 2 Cases / 대한산업의학회지

BACKGROUND: Mercury poisoning presents a variety of clinical pictures depending on the chemical structure, the route of exposure, the amount absorbed and other individual factors. Therefore, the ingestive and subcutaneous absorption of elemental(metallic) mercury can be considered to be relatively harmless in contrast to the inhalation of mercury vapor. CASE REPORTS: A 72-year-old man presented to the department of urology due to tenderness, edema and a necrotic abscess of his penis after trauma. The soft tissue abscess required a surgical resection of the penis. For chelation therapy, oral D-penicillamine was administrated. 7 months later, he showed no subjective or objective signs of mercury poisoning. Another 5-yearold girl presented to the emergency department after accidental self-ingestion of elemental mercury. She was followed clinically and did not show any systemic mercury poisoning. CONCLUSION: The Mercury concentrations in the blood and urine were elevated in the case of subcutaneous exposure, but was unchanged in the case of ingestion. Subcutaneous and gastrointestinal exposure to metallic mercury has a minimal risk for systemic mercury poisoning, which is in contrast to the exposure by inhalation.

A Case of Minimal Change Nephrotic Syndrome Associated with D-penicillamine Therapy of Wilson's Disease / 대한소아소화기영양학회지

Wilson's disease is a treatable autosomal recessive inherited disorder of copper metabolism due to mutation of the copper transporting gene. The basic strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both a low copper diet and copper-chelating agents. D-penicillamine is the first choice as a copper-chelating agent. Some serious side effects could occur in 3~5% of all patients following D-penicillamine therapy. We report a 19 year-old male with Wilson's disease who developed nephrotic syndrome 6 months after the initiation of D-penicillamine therapy. Prednisolone was administered to control nephrotic syndrome and D-penicillamine was switched to trientine. Urinary remission was achieved within a week and maintained thereafter. Nephrotic syndrome was proven to be MCNS by kidney biopsy.

A case of myasthenia gravis in a patient with diffuse systemic sclerosis developed during D-penicillamine treatment / 대한류마티스학회지

D-penicillamine has been used to reduce skin thickening and prevent the development of significant organ involvement in the treatment of scleroderma. This drug has a number of serious adverse reactions including glomerulonephritis with nephrotic syndrome, aplastic anemia, thrombocytopenia, and myasthenia gravis. A 44-year-old woman was admitted for weakness of the extremity muscle during repeated use. Eight months before admission, she visited dermatology department of our hospital. She was diagnosed as having scleroderma. D-penicillamine was started for the treatment of skin lesions. Based on the fluctuation of proximal muscle weakness, high titer of acetylcholine receptor antibody and definite decremental response of Jolly test, she was diagnosed as myasthenia gravis. D-penicillamine was discontinued because of the suspicion of D-penicillamine induced myasthenia gravis. Muscle weakness improved after D-penicillamine was withdrawn. The development of reversible myasthenia gravis may be regarded as a part of general predisposition for autoimmune disease related to the D-penicillamine therapy.

Regulation of type I collagen and interstitial collagenase mRNA expression in human dermal fibroblasts by colchicine and D-penicillamine

Sclerosis is a disease process in which idiopathic hardening occurs in the skin and/or internal organs as a result of the accumulation of type I collagen, induced mainly by transforming growth factor-beta. Colchicine and D-penicillamine are widely used for its treatment. Their effects are known to be due to post-translational down-regulation of type I collagen synthesis, with colchicine also up-regulating interstitial collagenase. To determine whether or not they have any pre-translational effect on type I collagen and MMP-1, and also to observe their effects on the action of TGF-beta, cultured neonatal foreskin fibroblasts were treated with colchicine and D-penicillamine, singly and together. The amount of type I collagen and MMP-1 mRNA were quantitated by Northern blot hybridization. Colchicine suppresses the basal level of type I collagen mRNA but minimally stimulates the mRNA expression of MMP-1, whereas D-penicillamine does not have any significant effects on either. Colchicine was also able to significantly suppress the TGF-beta-induced up-regulation of type I collagen mRNA expression.

Two Cases of Wilson's Disease Associated with Kayser-Fleicher Ring

Wilson's disease is an inborn error of copper metabolism which may be associated with hepatic cirrhosis and progressive degeneration of the central nervous system. The most common ophthalmologic finding in Wilson's disease is the Kayser-Fleischer ring. Other much less common physical signs include neurologic signs, endocrinologic abnormality. The Kayser-Fleischer ring occurs in the corneal periphery and is usually yellow- brown color. The Kayser-Fleischer ring.copper deposition at the level of the posteior position of Descemet's membran. The authours have recently experienced two cases of wilson's disease. One case. a 20-year-old girl, has Kayser-Fleischer rings in both eyes, amenorrhea, chronic active hepatitis and the other case, a 21-years-old girl, has dense yellow-green colored Kayser-Fleischer rings in both eyes, palilalia, and family relationship. Both cases have been treated with D-penicillaine and low copper diet. After treatment, clinical manifestation have been improved markedly at former case and the other cae is steady stage, but the Kayse-Fleischer rings have not disappeared yet in both cases.