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 patien...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.展开更多
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. ...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.展开更多
AIM: To study the effect of anti-copper treatment for survival of hepatic cells expressing different ATP7 B mutations in cell culture. METHODS: The most common Wilson disease(WD) mutations p.H1069 Q, p.R778 L and p.C2...AIM: To study the effect of anti-copper treatment for survival of hepatic cells expressing different ATP7 B mutations in cell culture. METHODS: The most common Wilson disease(WD) mutations p.H1069 Q, p.R778 L and p.C271*, found in the ATP7 B gene encoding a liver copper transporter, were studied. The mutations represent major genotypes of the United States and Europe, China, and India, respectively. A human hepatoma cell line previously established to carry a knockout of ATP7 B was used to stably express WD mutants. m RNA and protein expression of mutant ATP7 B, survival of cells, apoptosis, and protein trafficking were determined.RESULTS: Low temperature increased ATP7 B protein expression in several mutants. Intracellular ATP7 B localization was significantly impaired in the mutants. Mutants were classified as high, moderate, and no survival based on their viability on exposure to toxic copper. Survival of mutant p.H1069 Q and to a lesser extent p.C271* improved by D-penicillamine(DPA) treatment, while mutant p.R778 L showed a pronounced response to zinc(Zn) treatment. Overall, DPA treatment resulted in higher cell survival as compared to Zn treatment; however, only combined Zn + DPA treatment fully restored cell viability. CONCLUSION: The data indicate that the basic impact of a genotype might be characterized by analysis of mutant hepatic cell lines.展开更多
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...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).展开更多
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 t...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.展开更多
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 particul...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?展开更多
Background: Diabetes insipidus (DI) is a rare disorder characterized by inappropriate polyuria and hypo-osmolar urine. It is caused by inadequate production of antidiuretic hormone, in response to hypothalamic osmorec...Background: Diabetes insipidus (DI) is a rare disorder characterized by inappropriate polyuria and hypo-osmolar urine. It is caused by inadequate production of antidiuretic hormone, in response to hypothalamic osmoreceptor-stimulation, from the pituitary gland (central DI) or resistance to its action at terminal distal convoluted tubules and collecting ducts (nephrogenic DI). Most cases of nephrogenic DI are caused by drugs, especially chronic lithium use. The Case: A 46-year-old man manifested such a disorder 8 months following d-Penicillamine (d-P) therapy for cystinuria. The drug was discontinued and the patient was managed conservatively with high fluid intake, diet low in protein and salt as well as alkalization of urine with Urolyte U to a pH > 7.5. Six weeks later, such side effect disappeared. Our patient had developed such phenomenon: a) without significant liver or renal disease to account for cumulative toxicity, and b) with a conventional dosage range of d-P. Such isolated toxicity indicates inherited a predisposition to this side effect. Conclusion: DI is a potential side effect of d-P therapy that is nephrogenic in site, transient in prognosis and an isolated phenomenon likely to reflect genetic predisposition.展开更多
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 ...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.展开更多
文摘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.
文摘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.
文摘AIM: To study the effect of anti-copper treatment for survival of hepatic cells expressing different ATP7 B mutations in cell culture. METHODS: The most common Wilson disease(WD) mutations p.H1069 Q, p.R778 L and p.C271*, found in the ATP7 B gene encoding a liver copper transporter, were studied. The mutations represent major genotypes of the United States and Europe, China, and India, respectively. A human hepatoma cell line previously established to carry a knockout of ATP7 B was used to stably express WD mutants. m RNA and protein expression of mutant ATP7 B, survival of cells, apoptosis, and protein trafficking were determined.RESULTS: Low temperature increased ATP7 B protein expression in several mutants. Intracellular ATP7 B localization was significantly impaired in the mutants. Mutants were classified as high, moderate, and no survival based on their viability on exposure to toxic copper. Survival of mutant p.H1069 Q and to a lesser extent p.C271* improved by D-penicillamine(DPA) treatment, while mutant p.R778 L showed a pronounced response to zinc(Zn) treatment. Overall, DPA treatment resulted in higher cell survival as compared to Zn treatment; however, only combined Zn + DPA treatment fully restored cell viability. CONCLUSION: The data indicate that the basic impact of a genotype might be characterized by analysis of mutant hepatic cell lines.
基金Project supported by Shandong Province Education Bureau (J06060)
文摘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).
基金supported by the NIH–Research Centers at Minority Institutions (G12MD007591)the projects CTQ201678793-P (MINECO of Spain)+2 种基金PEIC-2014-001-P (Junta de Comunidades de Castilla-La Mancha, JCCM)MINECO of Spain for the predoctoral (BES-2011-045438)stay (EEBB-I-15-10091) grants
文摘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.
文摘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?
文摘Background: Diabetes insipidus (DI) is a rare disorder characterized by inappropriate polyuria and hypo-osmolar urine. It is caused by inadequate production of antidiuretic hormone, in response to hypothalamic osmoreceptor-stimulation, from the pituitary gland (central DI) or resistance to its action at terminal distal convoluted tubules and collecting ducts (nephrogenic DI). Most cases of nephrogenic DI are caused by drugs, especially chronic lithium use. The Case: A 46-year-old man manifested such a disorder 8 months following d-Penicillamine (d-P) therapy for cystinuria. The drug was discontinued and the patient was managed conservatively with high fluid intake, diet low in protein and salt as well as alkalization of urine with Urolyte U to a pH > 7.5. Six weeks later, such side effect disappeared. Our patient had developed such phenomenon: a) without significant liver or renal disease to account for cumulative toxicity, and b) with a conventional dosage range of d-P. Such isolated toxicity indicates inherited a predisposition to this side effect. Conclusion: DI is a potential side effect of d-P therapy that is nephrogenic in site, transient in prognosis and an isolated phenomenon likely to reflect genetic predisposition.
基金Supported by National Natural Science Foundation of China:Study on the Effect of Gandou Tablets in Mitophagy by Willson Disease Model TX Mouse(No.81503443)
文摘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.
