succimer and Hepatolenticular-Degeneration

Dimercaptosuccinic acid (DMSA) therapy is a kind of chelation therapy for patients with Wilson 's disease (WD). While there have been reports of side effects associated with DMSA, the development of membranous nephropathy as a result of this therapy is uncommon.. We present a case of a 19-year-old male patient with Wilson's disease who experienced proteinuria while receiving long-term DMSA treatment. Further evaluation revealed abnormally low levels of serum ceruloplasmin and serum albumin, as well as a 24-hour urinary protein excretion of 4599.98 mg/24 h. A renal biopsy confirmed the presence of membranous nephropathy. After ruling out other potential causes, we determined that the patient's membranous nephropathy was likely caused by DMSA. Following treatment with glucocorticoids, there was a significant reduction in proteinuria.. This case highlights the possibility of DMSA-induced membranous nephropathy and the importance of considering this diagnosis in patients receiving DMSA treatment. Given the widespread use of DMSA in the treatment of Wilson's disease, further research is needed to fully understand the potential role of this drug in the development of membranous nephropathy.

Topics: Adult; Copper; Glomerulonephritis, Membranous; Hepatolenticular Degeneration; Humans; Male; Proteinuria; Succimer; Young Adult

Wilson's disease (WD), also called hepatolenticular degeneration, is an autosomal recessive inheritance disorder of copper metabolism characterized by the multiple mutations in the ATP-ase 7B gene of chromosome 13q. About half of the WD patients have neurological or psychiatric symptoms. As WD is a kind of medicable or nearly curable neurodegenerative disease in the field of medicine, early consideration/examination and without delay/ life-long treatment usually lead to better prognoses. The drugs, also named as anticopper agents, are commonly used in clinics including D-penicillamine, trientine, sodium dimercaptosuccinate, dimercaptosuccinic acid, zinc and tetrathiomolybdate. This provides detailed reviews about these medicines.

Topics: Chelating Agents; Copper; Hepatolenticular Degeneration; Humans; Medicine, Chinese Traditional; Molybdenum; Penicillamine; Succimer; Treatment Outcome; Trientine; Zinc

To compare the effects of Gandou I (GD, a Chinese herbal preparation) and dimercaptosuccinate acid (DMSA) in treating Wilson disease (WD).. Ninety-four patients with WD were divided into 2 groups, 32 cases in the GD group and 62 in the DMSA group, they were treated with GD and DMSA respectively. The therapeutic course was 4 weeks for both groups. Modified Goldstein's Degree was adopted to evaluate the clinical effect.. The total effective rate of the GD group was 71.9%, which was similar to that of the DMSA group (77.4%, P > 0.05). But the adverse reaction occurred in the latter group was more than that in the former.. GD is a low toxic and highly effective drug for long-term treatment of WD.

Topics: Adolescent; Adult; Chelating Agents; Child; Drugs, Chinese Herbal; Female; Hepatolenticular Degeneration; Humans; Male; Succimer; Tablets

To investigate the curative effect of integrated traditional and western medicine (TCM-WM) therapy on hepatolenticular degeneration (HLD).. Eighty patients with HLD were divided randomly into two groups (TCM-WM group and WM group), TCM-WM group (40 cases) were given orally dimercaptosuccinic acid (DMSA) and Gandou ([symbol: see text]) decoction for 1 month. The efficacy was compared with that of 40 cases treated with DMSA as the control. The changes of urinary trace and macro-elements before and after treatment were observed.. The total effective rate of TCM-WM group was significantly higher than that of WM group (P < 0.05), especially more patients with hepatic type responded well to treatment with TCM-WM than with only chelating agent DMSA. Urinary trace and macro-elements were all obviously elevated in patients of two groups after treatment (P < 0.01).. TCM-WM therapy appears extremely promising as new cupruretic method for treatment of HLD. It is particularly suitable for treating the patient with hepatic type.

Topics: Adolescent; Adult; Chelating Agents; Child; Copper; Drugs, Chinese Herbal; Female; Hepatolenticular Degeneration; Humans; Male; Succimer

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism characterized by liver and central nervous system dysfunction. Considerable evidence suggests that infertility is also very common in male patients with WD, but the exact molecular mechanisms involved remain unknown. In order to further investigate the pathological changes in the hypothalamic-pituitary-testicular (HPT) axis and its mechanisms, mice were divided into the normal control group (NC), WD model TX mice group (WD), dimercaptosuccinic acid-treated TX mice group (DMSA), and pregnant horse serum gonadotropin-treated TX mice group (PMSG). The copper content and morphology of hypothalamus and pituitary tissues, the ultrastructure and apoptosis of hypothalamus neurons and pituitary gonadotropin cells, the serum levels of reproductive hormones, and the pregnancy rate and litter size of the female mice were studied. The expression of apoptosis-related proteins and the phosphorylation of extracellular regulatory protein kinase (ERK) 1/2 in the hypothalamus and pituitary were detected. The results showed that the copper content was significantly increased in the WD group, and the histopathological morphology and ultrastructure of the hypothalamus and pituitary were damaged. The levels of the gonadotropin-releasing hormone, the follicle-stimulating hormone, the luteinizing hormone, and testosterone were significantly decreased. The apoptosis rate in the hypothalamus and pituitary was significantly increased. The expressions of proapoptotic proteins Bax and Caspase-3 were significantly increased, the expression of the anti-apoptotic protein Bcl-2 was significantly decreased, and the phosphorylation level of ERK1/2 was significantly decreased. Fertility is significantly reduced. After DMSA intervention, the hypothalamus tissue copper content decreased, the hypothalamus and pituitary tissue morphology and ultrastructure were improved, cell apoptosis was alleviated, the expression of Bax and Caspase-3 was significantly decreased, the expression of Bcl-2 was significantly increased, and the reproductive hormone level, phosphorylation level, and fertility were increased. Fertility was preserved after treatment with PMSG in male TX mice. These results suggest that copper deposition in WD causes male fertility decline by impairing reproductive neuroendocrine hormone release through inducing apoptosis and inhibiting the ERK signal in the hypothalamic-pituitary region. This study can also

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Copper; Female; Fertility; Gonadotropins, Pituitary; Hepatolenticular Degeneration; Horses; Hypothalamus; Luteinizing Hormone; Male; Mice; Pregnancy; Protein Kinases; Succimer

The clinical data of safety and efficacy of a combined treatment with dimercaptosuccinic acid (DMSA) and Zinc with 2 years' follow-up in 60 neurological Wilson's disease (WD) patients was retrospectively analyzed. All the patients included in the present study were newly diagnosed and initialized with D-penicillamine (DPA) treatment but were found to have either neurological deterioration or allergy, and their treatment was switched to a combined treatment of DMSA and Zinc. Fifty-one patients (85%) had the neurological symptoms improved 1 and 2 years after treatment, 7 (11.67%) experienced a stable neurological condition, and 2 (3.33%) suffered deterioration of neurological symptoms. No early neurological deterioration was observed in all patients. Twenty-five percent patients experienced mild adverse reactions which did not require a discontinuation of the DMSA and Zinc treatment. Our study confirmed the safety and efficacy of the combined DMSA and Zinc therapy as an initial and probably long-term treatment in neurological WD patients.

Topics: Adolescent; Adult; Brain; Chelating Agents; Child; Disease Progression; Drug Hypersensitivity; Drug Substitution; Drug Therapy, Combination; Female; Hepatolenticular Degeneration; Humans; Male; Penicillamine; Retrospective Studies; Succimer; Time Factors; Treatment Outcome; Young Adult; Zinc

Wilson disease (WD) is an autosomal-recessive disorder associated with the impaired copper metabolism, resulting in hepatic and neurologic manifestations. D-Pencillamine (DPA) is a first-line of treatment however, monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA), is gaining recognition recently as a future chelating agent of choice. We evaluated the effects of MiADMSA against copper-induced (20 mg/kg, orally, once, daily for 16 weeks) hepatic and immunological changes in the male Sprague Dawley (SD) rats. Copper overload increased the levels of pro-oxidant and concurrently decreased the levels of antioxidant enzymes in the liver. Increased oxidative stress triggered the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in the liver and down-regulated the anti-inflammatory cytokine IL-4. Altered liver function parameters as well as serum immunoglobulins' (IgG, IgA, IgE, and IgM) levels, were also noted. MiADMSA treatment restored most of copper altered biochemical and immunological changes. Further, the histopathological changes proved that MiADMSA treatment ameliorated copper induced hepatic injury. Infra red spectra of liver tissue indicated shift in the characteristic -OH peak during copper exposure while the shifting came to normal in MiADMSA administered rat liver. We conclude that MiADMSA could be a promising antidote for the chronic copper toxicity and possibly in the clinical management of WD.

Topics: Animals; Chelating Agents; Copper; Cytokines; Hepatolenticular Degeneration; Humans; Interleukin-1beta; Interleukin-6; Liver; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Succimer

To compare the clinical symptoms, brain copper deposition changes of Meso-2,3-dimercaptosuccinic acid (DMSA) and penicillamine therapy in patients with Wilson disease (WD) within 2 years.. 68 drug-naive patients with WD were enrolled. 10 WD patients treated with zinc gluconate alone were used as the control group. Neurological symptoms were scored using the modified Young Scale. Liver function tests, copper indices and sensitive weighted imaging (SWI) examination were collected. The values of corrected phase (CP) were collected. WD patients were treated with DPA (group 1) or DMSA (group 2) for two years, and followed up every 2 months.. The ratio of neurological improvement in group 2 was higher than that in group 1 (P = 0.029). Higher rate of neurologic worsening was noticed in patients treated with DPA vs DMSA (P = 0.039). The post-treatment neurological score of DMSA group was lower than that of Zn group (P = 0.037). Hepatic function in 63.3% of patients was stable, while 16.7% was improved, and 20% was deteriorated, after DMSA therapy. Urinary copper levels were lower 1 month (p = 0.032), 4 months (p = 0.041), 12 months (p = 0.037) after initiation of treatment in group 2 than in group 1. At the first year of treatment, the CP values in globus pallidus and substantia nigra in group 2 were higher than those in group 1 (P = 0.034,0.039). At the second year of treatment, the CP values of substantia nigra in group 2 were higher (P = 0.041). Discontinuation was more common in patients on DPA therapy (P = 0 0.032).. DMSA could remove metal from brain tissue faster than DPA. DMSA is effective for neurologic symptoms, while the outcome for hepatic symptoms is not entirely satisfactory. DMSA therapy is better tolerated than DPA.

Topics: Adult; Brain; Chelating Agents; Copper; Female; Hepatolenticular Degeneration; Humans; Male; Penicillamine; Succimer; Young Adult

Topics: Chelating Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Hepatolenticular Degeneration; Humans; Integrative Medicine; Phytotherapy; Succimer; Treatment Outcome

To observe the biliary copper content of nonhepatolenticular degeneration (HLD) controls and changes in the trace elements in the bile, cerebrospinal fluid, blood and urine of hepatolenticular degeneration patients before and after dimercaptosuccinic acid (DMSA) treatment in order to further explore the etiological mechanism of HLD and prove the therapeutic effect of DMSA on HLD patients.. A consecutive series of 20 patients with HLD were given DMSA orally for 4 weeks. Adult dosage was 1.5 g/day and child dosage 1.0 g/day. Their bile, cerebrospinal fluid, blood and urine samples were obtained before and after treatment with DMSA through duodenal drainage and lumbar puncture. Biliary samples of 22 non-HLD controls were taken by drainage tube after surgical operation. Hitachi-208 atom absorption spectrophotometer was used to assay the content of copper, zinc and iron of each sample.. DMSA could effectively improve the symptoms such as dysphasia, salivation, dysphagia and darkening of the skin; limb trembling and myotonia came second; but it showed no obvious effect on dysstasia, limb contracture and deformity, and hepatosplenomegaly. It was effective for the patients who were younger and had no obvious hepatic damage. No serious side effects were seen through the course of treatment. Laboratory study showed that biliary copper content of HLD patients was evidently lower than that of non-HLD controls (P < 0.01); DMSA could evidently improve biliary copper excretion besides clearly increase urinary copper excretion (P < 0.01) and had nothing to do with biliary zinc excretion (P > 0.05).. Biliary copper excretion disturbance participates directly in the pathophysiology of copper retention of HLD patients. DMSA is a favorable cupruretic drug for patients with HLD.

Topics: Adolescent; Adult; Antidotes; Bile; Child; Copper; Female; Hepatolenticular Degeneration; Humans; Iron; Male; Succimer; Trace Elements; Zinc

To observe the effect of combination therapy of traditional and Western medicine (TCM-WM) on brainstem auditory evoked potential (BAEP) in hepatolenticular degeneration patients.. BAEP was recorded and analyzed in 65 patients with hepatolenticular degeneration (HLD) before and after decoppered TCM-WM treatment.. The peak latency (PL) and interpeak latency (IPL) of BAEP in untreated patients were greatly increased compared with those of control group, especially in the prolongations of III, V, III- V and I-V. The PL and IPL improved as improvement of clinical symptoms in HLD patients treated with TCM-WM than that in untreated patients. The abnormal rates of men and women in BAEP were decreased from 21.97% and 19.05% in untreated patients to 9.09% and 6.75% in treated patients respectively.. BAEP not only has an complementary diagnosis but also judge the efficacy of treatment on the HLD disease.

Topics: Adolescent; Adult; Chelating Agents; Child; Drugs, Chinese Herbal; Evoked Potentials, Auditory, Brain Stem; Female; Hepatolenticular Degeneration; Humans; Male; Penicillamine; Succimer

Intelligence quotient (IQ) of 28 hepatic lenticular degeneration (HLD) patients was analysed with Wechsler Adult Intelligence Scale-revised by China (WAIS-RC) before and after two months treatment by the HLD-Relief decoction supplemented with copper-clearing drug, and the result was compared with that of 30 healthy persons for control. The results showed that the Vocable IQ (VIQ), Performance IQ(PIQ) and Full IQ(FIQ) of HLD patients were markedly lower than that of control (P < 0.005), especially in visual space disorder, which indicated that the copper ion depositing in patient's brain not only damaged neuronic motorial functions but also produced a marked effect on the patient's intelligence. After treatment, the total intelligential level including VIQ, PIQ and FIQ has been raised, particularly in PIQ in which all scores were obviously increased (P < 0.001). It was also showed that the damage of intelligence in HLD patient became more serious as the course of disease was prolonged and the early treatment facilitated the IQ level to approach the normal criterion. It indicated that the treatment with combined therapy is effective to the intelligence and extrapyramidal symptoms in HLD patients.

Topics: Adolescent; Adult; Chelating Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Hepatolenticular Degeneration; Humans; Intelligence; Male; Penicillamine; Prospective Studies; Succimer; Wechsler Scales

From 1974 to 1988, 418 cases of Wilson's disease were treated with TCM-WM in our hospital. 147 cases were of Wilson's type; 149 cases were of pseudosclerosis type; 40 cases were of abdominal and hepatocerebral type; 21 cases were of choreoathetosis type and 21 cases of other types. After a course of treatment for 3 to 6 months, 103 patients showed marked improvement and 286 made some improvement, but no effect was found in 22 patients and 7 deaths were observed. The results were as follows: (1) The mortality in the severe and moderate groups were significantly higher than the mild (P less than 0.05) and the marked effective rate was less than the latter (P less than 0.01). (2) The marked effective rate was lower in abdominal and hepatocerebral type, and no significant difference was found in recovery rate between Wilson's type and pseudosclerosis type.

Topics: Adolescent; Adult; Child; Child, Preschool; Combined Modality Therapy; Drugs, Chinese Herbal; Female; Hepatolenticular Degeneration; Humans; Male; Middle Aged; Penicillamine; Succimer; Sulfates; Sulfhydryl Compounds; Zinc; Zinc Sulfate