Clinical Efficacy and Safety of Chelation Treatment with Typical Penicillamine in Cross Combination with DMPS Repeatedly for Wilson's Disease

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine （PCA） in cross combination with sodium 2, 3-dimercapto-l-propane sulfonate （DMPS） repeatedly in patients with Wilson＇s disease （WD）. Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocy- topenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Im- proved or recovered liver fimction in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up pe- riod of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maitain lifelong therapy.

Comparison of long-lasting therapeutic effects between succimer and penicillamine on hepatolenticular degeneration

AIM To compare the long term effect of succimer (Suc) with that of penicillamine (Pen) in treating hepatolenticular degeneration (HLD). METHODS One hundred and twenty patients with HLD were divided into 2 groups. Group A ( n =60) received Suc 750mg , po. bid. Group B ( n =60) received Pen 250mg , po. qid. The period of maintenance treatment varied from 6 months to 3 years, averaging 1 5 years. Symptoms and therapeutic effects were evaluated by modified Goldstein scale. RESULTS The total effectiveness of group A in two different periods of treatment were 80% and 85% respectively, higher than those of group B (58% and 59% respectively) ( P <0 05). Suc also had obvious curative effects for the patients who failed in the use of Pen. There were fewer side effect in group A than in group B ( P <0 05). Suc and Pen could increase urinary copper excretion effectively and continually. CONCLUSION Suc is more effective and safer than Pen. Clinically, it can replace Pen as first choice drug for long term maintenance therapy of HLD.

Flow-Injection Enhanced Chemiluminescence Method for Determination of Penicillamine

A new flow-injection procedure has been developed for the determination of penicillamine based on the enhancement of the chemiluminescence(CL) reaction of the penicillamine-cerium(Ⅳ)-hydrocortisone system. The method was simple, selective and sensitive with a detection limit of 6.2×10-5 mol·L-1(S/N=3). It was applicable to the determination of penicillamine in the concentration range of 2×10-6～5×10-4 mol·L-1. The method was successfully applied to the determination of penicillamine in tablets. The relative standard deviation (RSD) was 1.42% (n=7) and the recovery was 97%～103% (n=4).

Analysis of penicillamine using Cu-modified graphene quantum dots synthesized from uric acid as single precursor

A simple methodology was developed to quantify penicillamine(PA) in pharmaceutical samples, using the selective interaction of the drug with Cu-modified graphene quantum dots(Cu-GQDs). The proposed strategy combines the advantages of carbon dots(over other nanoparticles) with the high affinity of PA for the proposed Cu-GQDs, resulting in a significant and selective quenching effect. Under the optimum conditions for the interaction, a linear response(in the 0.10–7.50 μmol/L PA concentration range) was observed. The highly fluorescent GQDs used were synthesized using uric acid as single precursor and then characterized by high resolution transmission electron microscopy, Raman spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, fluorescence, and absorption spectroscopy. The proposed methodology could also be extended to other compounds, further expanding the applicability of GQDs.

Penicillamine and auto-immunity:Relationship or coincidence?

Drug induced lupus is an established and recognised entity,and penicillamine is one of the drugs that induce it.But the uncertainty remains:Could penicillamine trigger autoimmunity in a broad-spectrum or in a particular way?

Clinical efficacy and safety of Gandouling plus low-dose D-penicillamine for treatment of Wilson's disease with neurological symptoms

OBJECTIVE： To investigate the effect and safety of Gandouling plus low-dose D-penicillamine for treating patients with Wilson＇s disease （WD） who have neurological symptoms. METHODS： WD patients with neurological symptoms were divided into two groups： a treatment group （n = 53） and a control group （n = 50）. The treatment group received anti-copper therapy with a combination of Gandouling and low-dose D-peni- cillamine （10 mglkg）, whereas the control group was with conventional dose D-penicillamine （20 rag/ kg） monotherapy. The clinical efficacies, adverse re- actions, and results of the various hematological and biochemical investigations were recorded and analyzed statistically. RESULTS： Overall, 98.11% of the WD patients treated with the combined therapy experienced alleviation of their neurological condition （paralleled by a significantly improved Global Assessment Scale score or remained stable）. Their white blood cell and platelet counts stabilized, and their liver function was improved or remained stable. The combined therapy also obviously promoted improved 24-h urinary copper excretion. Only 15.09% of the WD patients with the combined therapy experienced adverse reactions, including neurological deterioration in one case （1.89%） and hepatic worsening in one case （1.89%）, which was less frequent than that in the control group given conventional-dose D-penicillamine monotherapy. CONCLUSION： Treating WD patients with neurological symptoms using Gandouling plus low-close D-penicillamine is effective and safe.

Wilson's disease: A review of what we have learned

Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.

The Electrochemical Behavior of Au/Au NPs/PNA/ZnS e-QD/ACA Electrode Towards Cy SH Oxidation

This work describes the electrochemical behavior of azodicarboxamide(ACA) film immobilized on the surface of penicillamine(PNA)/Zn Se-quantum dot(Zn Se-QD) gold nanoparticle(Au NPs) Au electrode. Electrocatalytic activity of modified electrode toward the oxidation of cysteine(Cy SH) was investigated. The surface structure and composition of the sensor were characterized by scanning electron microscopy(SEM). Oxidation of Cy SH on the surface of modified electrode was investigated with cyclic voltammetry, electrochemical impedance spectroscopy(EIS),hydrodynamic voltammetry and chronoamperometry methods. The results show that the PNA/Zn Se-QD/ACA film displays excellent electrochemical catalytic activities towards Cy SH oxidation. The modified electrode shows reproducible behavior and high level of stability during the electrochemical experiments. Also it has short response time, low detection limit, high sensitivity and low operation potential, which can be used as an amperometric sensor for monitoring of Cy SH. The proposed modified electrode was successfully used for determination of Cy SH in real sample such as human serum.

Detection of Penicillin via Surface Plasmon Resonance Biosensor

A method of using Au colloid to capture the decomposed product of penicillin, penicillamine, on a surface plasmon resonance（SPR） biosensor for the quantitative determination of penicillin was developed. Based on the de-composition of penicillin to generate penicillamine and penilloaldehyde, a high sensitive biosensor for detecting penicillin was also developed. In our experiment, it was penicillamine rather than penicillin that has been measured. This is because penicillamine contains a functional group that makes it self-assembling on Au colloid to increase the molecular weight so as to improve the surface plasmon resonance signal. On a UV-Vis spectrophotometer, a high concentration of penicilliamine-Au complex was determined, indicating that penicillamine was already well combined with Au colloid. The method, using the combination of Au colloid with penicillamine, proved to detect penicillin.

Liver transplantation in Wilson's disease: Single center experience from Saudi Arabia

AIM: To determine liver transplantation outcomes in Wilson's disease (WD) patients, focusing on neurological manifestations. METHODS: This retrospective study assessed data from 16 WD patients (nine males, 56%) who had liver transplants between 1991 and 2007. Survival, graft function, and neurological complications were assessed during a follow-up period of up to 15 years. In addition, each patient's medical record was reviewed in detail to find the type of Wilson's disease (hepatic or hepatic plus neurological WD), indication for liver transplantation, use of chelating agents prior to transplantation, immediate and long term complications following transplantation, the donor details, and the pathology of explanted liver. RESULTS: End-stage liver disease was the indication for transplantation in all 16 WD patients. Four patients displayed WD-related neurological symptoms in addition to liver disease. Living-related liver transplantation was done in three cases. One patient died on postoperative day 6 due to primary graft non-function. Oneyear post liver transplant survival was 94%. Neurological manifestations of all four patients disappeared during their follow-up. Four patients developed acute cellular rejection, but all responded to treatment. One patient developed chronic ductopenic rejection after 15 years post-transplantation and their graft failed; this patient is currently waiting for re-transplantation. Fourteen patients (88%) are still living. The long-term average survival is currently 10.5 years, with a current median survival of 8 years. Long-term graft survival is currently 81%. CONCLUSION: Shortand long-term survival in WD patient liver transplantation was excellent, and neurological and psychological WD manifestations disappeared during long-term follow-up.