Enfermedad de Wilson: reporte de caso / Wilson's disease: case report

Antecedentes: La enfermedad de Wilson, también conocida como degeneración hepatolenticular, fue primeramente descrita por el neurólogo británico Kinnier Wilson en 1912. La prevalencia estimada de la enfermedad de Wilson es de 1 caso en 30,000 nacimientos en la mayoría de las poblaciones. Algu- nos estudios sugieren que hombres y mujeres son afectados por igual. Las manifestaciones clínicas de la enfermedad de Wilson son predominantemente hepáticas, neurológicas y psiquiátricas, y algunos pacientes pueden tener una combinación de ellas. Las Guías de Práctica Clínica de enfermedad de Wilson recomiendan penicilamina, trientina, zinc, tetratiomolibdato y dimercaprol como medicamentos. Caso clínico: Se presenta un caso clínico de paciente femenina de 32 años de edad que presentó temblor en miembros superiores, progresivo, bilateral de reposo e intención, que llegó a dificultarle la escritura. Dos meses después la paciente nota trastornos de la marcha, con torpeza, lateropulsión, y posición distónica de pie izquierdo, durante la evolución se agrega hipofonía y disfagia, tanto para só- lidos como líquidos, dificultando pero no impidiendo alimentación, además lentitud mental y trastorno de estado de ánimo. Se le indicó penicilamina y hubo mejoría en su sintomatología en las siguientes consultas. Conclusiones: El pronóstico para los pacientes que tienen buena adherencia al tratamien- to es excelente, incluso en algunos que ya tienen enfermedad hepática avanzada por la enfermedad...(AU)

Elastosis Perforans Serpiginosa: a D-penicillamine induced dermatoses in a patient with Wilson's disease

Long term use of D-penicillamine for Wilson's disease can be associated with many adverse reactions and systemic side effects. We report the case of a 28-year-old male patient diagnosed with Wilson's disease presenting with a serpiginous raised violaceous skin lesion in the anterior aspect of the neck over the last six months and two small papules with central umbilication during the last month. Histopathological examination of skin lesions demonstrated transepidermal perforating channel, and the Verhoeff's-van Gieson stain showed marked increase number of irregular serrated elastic fibers suggesting the diagnosis of D- penicillamine induced elastosis perforans serpiginosa.

A Pediatric Case of a D-Penicillamine Induced ANCA-associated Vasculitis Manifesting a Pulmonary-Renal Syndrome

D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.

Síndrome de Wilson: relato de caso / Wilson´s Disease: a case repor

Objetivos: Este relato descreve um distúrbio genético raro, denominado de Síndrome de Wilson, herdado em caráter autossômico recessivo, com sintomas muito facilmente confundidos com outras doenças. A causa básica responsável pelas manifestações clínicas é o acúmulo de cobre em diversos compartimentos do organismo humano, especialmente em locais como fígado, cérebro, rins e córneas, devido a mutações no gene ATP7B que codifica a Cu+2 ATPase, uma proteína transportadora de cobre que está localizada no complexo de Golgi dos hepatócitos. As alterações hepáticas podem se apresentar como hepatite crônica, cirrose e, mais raramente, hepatite fulminante. As alterações neurológicas são variáveis, predominando os sintomas extrapiramidais, tremores, distonia, disartria, alterações de humor, sintomas psiquiátricos e, se não tratada, diminuição progressiva da capacidade intelectual. Uma das características mais extraordinárias dessa síndrome é a grande variabilidade de manifestações fenotípicas em pacientes que possuem a mesma mutação. No diagnóstico da doença de Wilson são analisados diversos parâmetros bioquímicos, sendo eles: ceruloplasmina sérica, cobre sérico, excreção urinária de cobre e concentração hepática de cobre. Além disso, realiza-se exame oftalmológico com a observação de anéis de Kayser ­ Fleischer. A fim de complementar e facilitar o diagnóstico podem ser realizados estudos genéticos, visto que muitas vezes os sintomas e alterações laboratoriais podem estar associados a outras doenças. O tratamento baseia-se no uso de drogas quelantes do cobre. A Dpenicilamina é a droga de escolha, apesar do risco de piora neurológica em até 50% dos pacientes e dos diversos efeitos colaterais associados ao seu uso. Trientina e tetratiomolibdato são drogas alternativas, sendo a última escolhida para indivíduos com sintomas neurológicos. O zinco tem indicação em assintomáticos ou em terapia de manutenção. O tratamento precoce evita graves complicações. Relato de caso: Paciente de 14 anos de idade, natural de Poço Fundo-MG, procurou atendimento médico por apresentar episódios frequentes de paralisia facial, principalmente na região mandibular, que levava à disfagia e disfonia, além de irritabilidade e anormalidades na marcha. Foi submetida ao exame de ressonância magnética que mostrou "alteração de sinal simétrica nos corpos estriados bilateralmente, com sinais de edema dos putâmens e núcleos caudados, e atrofia dos globos pálidos. Diante do histórico familiar para a síndrome de Wilson, foi realizado o diagnóstico diferencial, por meio da concentração de sérica de ceruloplasmina e cobre sérico e urinário, que mostraram alterações típicas da síndrome de Wilson e a biomicroscopia ocular que constatou a presença do anel de Kayser-Fleischer. Conclusões: Ainda há um longo caminho a ser seguido no que se diz respeito ao diagnóstico precoce da Síndrome de Wilson. Nesse caso, a paciente não apresentou hepatopatia pregressa. Isso mostra que a doença nem sempre se apresenta da forma esperada, e reflete a dificuldade de estabelecer um diagnóstico precoce que possa impedir o surgimento dos primeiros sintomas. Todos os portadores da síndrome de Wilson necessitam de atendimento multidisciplinar, (AU)

Objectives: This report describes a rare genetic disorder, called Wilson's Disease, inherited in an autosomal recessive form, with symptoms very easily confused with other diseases. The underlying cause of the clinical manifestations is the accumulation of copper in various compartments of the human body, especially in places such as liver, brain, kidneys and corneas, due to mutations in the ATP7B gene encoding Cu + 2 ATPase, a copper carrier protein which is located in the Golgi complex of hepatocytes. Liver changes may present as chronic hepatitis, cirrhosis and, more rarely, fulminant hepatitis. Neurological changes are variable, predominantly extrapyramidal symptoms, tremors, dystonia, dysarthria, mood changes, and psychiatric symptoms, if not treated, progressive decrease in intellectual capacity. One of the most extraordinary characteristics of this syndrome is the great variability of phenotypic manifestations in patients who have the same mutation. In the diagnosis of Wilson's disease, several biochemical parameters are analyzed: serum ceruloplasmin, serum copper, urinary excretion of copper and hepatic copper concentration. In addition, an ophthalmologic examination is performed with Kayser-Fleischer rings observation. In order to complement and facilitate the diagnosis, genetic studies can be performed, since the symptoms and laboratory abnormalities can often be associated with other diseases. Treatment is based on the use of copper chelating drugs. D-penicillamine is the drug of choice, despite the risk of neurological worsening in up to 50% of patients and the various side effects associated with its use. Trientin and tetrathiomolybdate are alternative drugs, the latter being chosen for individuals with neurological symptoms. Zinc is indicated for asymptomatic or maintenance therapy. Early treatment prevents serious complications. Case report: A 14-year-old patient from Poço Fundo-MG sought medical attention because of frequent episodes of facial paralysis, especially in the mandibular region, leading to dysphagia and dysphonia, as well as irritability and gait abnormalities. She underwent magnetic resonance imaging (MRI), which showed "symmetrical signal changes in the bilaterally striatum, with signs of edema of the caudate nuclei and caudate nuclei, and atrophy of the pale globes." In view of the family history of Wilson's syndrome, a differential diagnosis was performed, by serum concentration of ceruloplasmin and serum and urinary copper, which showed typical changes in Wilson's syndrome and ocular biomicroscopy, which verified the presence of the Kayser-Fleischer ring. The patient did not present previous liver disease, showing that the disease does not always present as expected, and reflects the difficulty in establishing an early diagnosis that may prevent the emergence of the first symptoms. All patients with Wilson's syndrome require multidisciplinary care since it is a disease that can significantly affect various organs and systems (AU)

Wilson's disease: the 60th anniversary of Walshe's article on treatment with penicillamine / Doença de Wilson: o 60° aniversário do artigo de Walshe no tratamento com penicilamina

ABSTRACT This historical review describes Professor Walshe's seminal contribution to the treatment of Wilson's disease on the 60th anniversary of his pioneering article on penicillamine, the first effective treatment for the condition.

RESUMO Esta revisão histórica enfatiza a contribuição seminal do Professor Walshe no tratamento da doença de Wilson (DW), com o seu trabalho pioneiro sobre o uso de penicilamina, o primeiro tratamento efetivo do mundo, publicado 60 anos atrás.

Speckled pigmentation and palmoplantar keratoses leading to the mass detection of chronic arsenic poisoning

Arsenic is a known human carcinogen and skin manifestations are the earliest and most specific markers of chronic arsenic poisoning. A 43-year-old man from Luzon presented at the Section of Dermatology with a one-year history of hyperkeratotic papules and plaques on the palms and soles. Numerous round hypopigmented macules were scattered on the upper back. Initial 24-hour urine arsenic level was elevated at 288mcg/liter. The patient underwent successful chelation with N-acetylpenicillamine and the palmoplantar keratoses were treated with cryotherapy and topical 20% salicylic acid in white petrolatum. In cooperation with the Department of Health, a comprehensive health and environmental assessment was conducted in the affected communities. This case highlights the role of dermatologists in the diagnosis and management of this public health problem.

Synthesis and anti-intracellular Copper overload evaluation of Nanoconjugated D-penicillamine -Dendrimer in Wilson's model cells

Background and Objective: Wilson's disease [WD] is caused by mutation to the cooer-transporting gene ATP7B. Chelation therapy is the main protochol of treatment for patients with Wilson's disease. D-penicillamine is one of the well-known chelator agants which is used in WD treatment but it can not enter into the intracellular space.This study was done to evaluate the synthesis and anti-intracellular Copper overload evaluation of Nanoconjugated D-penicillamine -Dendrimer in Wilson's model cells

Methods: In this descriptive-analytic study, initially 0.01 mm polyethylene glycol [PEG] and 0.0018 mm citric acid, Dendrimer was synthesized. After purification by dialysis bag and lyophilization, lOmg dendrimer was conjugated to 3.3mg D-penicillamine. Nanoconjugated D-penicillamine-dendrimer was injected on Wilson's model cells. After incubation and centrifugation intracellular measurement of copper concentration and FTIR test were done

Results: Copper accumulation significantly reduced in the HepG2 WD cell by Nanoconjugated D-penicillamine - Dendrimer in compared to D-penicillamine [P<0.05]. Copper accumulation was determined to be 46.61, MTT assay showed no toxicological damage in HepG2 WD cell

Conclusion: Nanoconjugated D-penicillamine -Dendrimer can reduces intracellular concentration of Copper

D-penicillamine Induced Elastosis Perforans Serpiginosa / 대한피부과학회지

No abstract available.

Avaliação do olfato em pacientes com doença de Wilson / Smell analysis in patients with Wilson's disease

A Doença de Wilson (DW) é uma moléstia hereditária, caracterizada pela deficiência de excreção do cobre pelo fígado devido à mutação do gene A TP7B. O distúrbio do olfato ocorre com frequência em doenças neurodegenerativas como na doença de Parkinson (DP) e na doença de Alzheimer (DA). A análise do olfato tem sido utilizada como um instrumento útil no diagnóstico diferencial das diversas formas de parkinsonismo degenerativo, e, especialmente, na diferenciação entre DP e tremor essencial. O diagnóstico precoce na DW é a chave para o sucesso do tratamento. Na hipótese de haver comprometimento do olfato em fases iniciais da doença, esse poderia ser um dado a mais para auxiliar no diagnóstico. Até o presente, há apenas um estudo relacionando a DW com a disfunção do olfato. O objetivo deste estudo foi avaliar o olfato em um grupo de pacientes com DW e confrontar com grupo- controle. No presente estudo, foram analisados 37 portadores de DW com manifestação neurológica, 24 portadores de DW sem manifestação neurológica e 59 controles. Todos os indivíduos foram analisados com relação à idade, ao gênero, ao grau de escolaridade, ao uso de tabaco e ao miniexame do estado mental (MEEM), e os portadores de DW foram avaliados quanto ao tempo de doença, tratamento medicamentoso e escore neurológico. O olfato foi avaliado por meio do teste de identificação de odor 8niffin' 8ticks (88-16 canetas numeradas e quatro opções de resposta para cada uma). Vinte e quatro indivíduos eram pacientes da DW sem manifestação neurológica (45,83% do gênero feminino) e 37 pacientes apresentavam manifestações neurológicas (56,76% do gênero masculino). O qrupo-controle foi composto por 59 indivíduos, 35 (59,33%) do gênero masculino. As médias de- idade foram de 33,38 ± 9,79 anos no grupo de portadores de DW com manifestação neurológica; 29 ± 9,61 anos no grupo de portadores de DW sem manifestação neurológica e 33,81 ± 10,67 anos no grupo-controle. Todos os pacientes com DW estavam em...

Wilson's disease (WO) is a hereditary disease due to a mutation in ATP7B gene, characterized by deficiency of copper excretion by the liver. Smell disorders are frequently encountered in neurodegenerative diseases, such as Parkinson's disease (PO) and Alzheimer's disease (AO). Smell analysis has been a useful tool for the differential diagnosis of several forms of degenerative parkinsonism, and especially for the differentiation between PO and essential tremor. Early diagnosis in WO is the key for a successful treatment. If there were smell impairment in the early stages of the illness, it could be used as another clue to help on its diagnosis. To the present date, there is only one study connecting WO with smell problems, the aim of this study was to evaluate smell function in a group of WO patients and compare them with a control group. We analyzed 37 WO patients with and 24 WO patients without neurologic symptoms, and 59 controls. Ali subjects were evaluated regarding age, gender, schooling, tobacco use, Mini Mental State Examination (MMSE), and the WO patients were also evaluated regarding duration of the illness, medication and neurologic scoring. Smell was analyzed by means of Sniffin' Sticks smell identification test (SS-16 numbered pens and four options of answer for each pen). Twenty-four subjects with WO had no neurologic symptoms (45.83% female), and 37 patients had neurologic impairment (56,76% male). The control group was composed by 59 individuais, 35 (59,33%) male. Their age average were 33,38 ± 9,79 years for WO neurologic symptoms; 29 ± 9,61 years for WO without neurologic symptoms; and 33,81 ± 10,67 years for the control group. Ali WO patients were on treatment: 47(77%) with penicillamine, 7(11,5%) with trientine, and 7(11,5%) with zinc salt formulations. The average of correct answers in the SS-16 were: 12,03 ± 2,21 for the WO with neurologic symptoms group; 12,15 ± 2,07 for the WO without neurologic symptoms; and...

Elastosis perforante serpiginosa y pseudo-pseudoxantoma elástico secundarias y tratamiento con D- penicilamina en paciente con enfermedad de Wilson / Elastosis perforans serpiginosa and pseudo-pseudoxanthomaelasticum secondary to D-penicillamine in a patient with Wilson’s disease

La D-penicilamina es la opción terapéutica más utilizada en la enfermedad de Wilson, rara enfermedad genética, autosómica recesiva, en la cual existe una alteración en el metabolismo del cobre que se deposita en los tejidos (hígado, encéfalo y córnea). Presenta numerosos efectos adversos, la mayoría cutáneos, que se observan cuando la droga es utilizada en altas dosis y por largo tiempo; entre ellos se encuentran las dermatosis degenerativas, que incluyen elastosis perforante serpiginosa, cutis laxa, anetodermia y pseudo-pseudoxantoma elástico (también llamado pseudoxantoma elástico símil o pseudoxantoma elástico like). Se presenta una paciente de 29 años con antecedentes de enfermedad de Wilson asociada a elastosis perforante serpiginosa y pseudo-pseudoxantoma elástico, ambas secundarias al tratamiento con D-penicilamina.

Penicillamineis the most commonly used therapeutic option in Wilson's disease.This is a rare, genetic, autosomal recessive diseasein which there is an alteration inthe metabolism of copper that is deposited in the tissues (liver, brain and cornea).It has numerous adverse effects, most of them affecting skin, but they are onlyobserved when the drug is used in high doses and for a long time, such as perforatingelastosis serpiginosa, cutis laxa, anetodermia and pseudo-pseudoxantomaelasticum (also called elasticum pseudoxantoma simil or elasticum pseudoxantomalike). We present the case of a29 year-old woman with a history of Wilson's diseaseand two concomitant degenerative dermatoses: elastosis perforans serpiginosa andpseudo pseudoxanthoma elasticum, both of them, secondary to treatment with Dpenicillamine.

Wilson's Disease in Bangladeshi Children: Analysis of 100 Cases / 대한소아소화기영양학회지

PURPOSE: To evaluate clinical and laboratory profile of Wilson's disease (WD) in children. METHODS: This cross sectional study was conducted at Bangabandhu Sheikh Mujib Medical University Hospital. Bangladesh, over a period of 3 years. One hundred consecutive children of WD between 3 to 18 years of age were evaluated. RESULTS: Mean age was 8.5+/-1.5 years. Male female ratio was 2:1. Ninety-one percent of patients were Muslim and 9% Hindu. A total of 53% cases of hepatic WD presented between 5 to 10 years of age and most of the neurologic WD manifested in 10-15 years age group. Sixty-nine children presented only with hepatic manifestations, 6 only with neurological manifestations, 14 with both hepatic and neurological manifestation, 10 children was asymptomatic and 1 patient presented with psychiatric features. WD presented as chronic liver disease (CLD) in 42%, CLD with portal hypertension in 34%, acute hepatitis in 20% and fulminant hepatic failure in 4% cases. Stigmata of CLD were found in 18% patients. Keiser-Fleischser ring was found in 76% total patients. Elevated serum transaminase was found in 85% cases, prolonged prothrombin time in 59% cases and hypoalbuminaemia in 53% cases. A total of 73% patients had low serum ceruloplasmin, basal urinary copper of >100 microg/day was found in 81% cases and urinary copper following penicillamine challenge of >1,200 microg/day was found in 92% cases. CONCLUSION: Majority of studied WD children presented with hepatic manifestation of which 76% presented with CLD. Any child presented with jaundice after the age of 3 years should be investigated for WD.

Penicillamine-induced toxic epidermal necrolysis in a patient with Wilson disease

Toxic epidermal necrolysis (TEN) is rare but life-threatening severe cutaneous adverse reaction, which is mostly induced by drugs. It characterized by widespread epidermal necrosis, resulting in bullae with sloughing and frequent involvement of the mucous membrane. Due to high mortality, management of patients requires prompt withdrawal of the causative drug, appropriate supportive care, and consideration of immune-modulating agents, such as intravenous immunoglobulin or corticosteroids. Wilson disease is an inherited disorder of copper transport that results in excessive accumulation of copper in the body. Copper chelation with penicillamine is an effective first line therapy in most patients. We present a 20-year-old man with Wilson disease who developed TEN following administration of penicillamine. He was successfully treated with systemic corticosteroid, intravenous immunoglobulin, and supportive management.

Mercury exposure of gold mining workers in the northwest of Iran

Mercury exposure is a health concern in the occupational settings like gold mining and chloralkali industries and blood and urine levels of mercury are used as exposure indicators. In this study, blood and urine concentrations of mercury were determined using hydride generation atomic absorption spectrophotometery [HGAAS] in sixteen gold miners with neuropsychiatric symptoms. The patients treated with two chelating agents, dimercaprol and D-penicillamine. The mean serum mercury levels before and after chelation therapy were 208.14 Micro g/L[-1] and 10.50 Micro g/L[-1], respectively. The mean urinary mercury levels before and after chelation therapy were 134.70 Micro g/L[-1] and 17.23 Micro g/L[-1], respectively. The results of this study showed that there are significant differences between concentration of blood and urine mercury before and after intervention [p<0.005]. There were no significant differences between in the biochemistry parameters of patients before and after treatment. This study indicated that the gold miners in the northwest of Iran had been exposed to high levels of mercury vapors [Hg[0]]

A Case of Skin Sclerosis Associated with Docetaxel Chemotherapy for Non-Small Cell Lung Cancer

A 64-year-old woman was diagnosed with non-small cell lung cancer. Her disease was stage 4 (T2N2M1) with squamous cell carcinoma. She had been treated with docetaxel and carboplatin. After a completion of 11 cycle of chemotherapy, edema appeared on both feet and had spread rapidly up to the pretibial area without response to diuretics. Sclerotic changes and pigmentation followed but both knees and other parts of the body were spared. There was no evidence of vascular occlusions. On serologic tests, antinuclear, anti-centromere, and anti-topoisomerase I antibodies were all negative. A skin biopsy revealed diffuse infiltration of lymphocytes and discretely thickened collagen bundles in the superficial dermis. After discontinuing docetaxel chemotherapy, she was treated with prednisolone and D-penicillamine and sclerotic changes on the lower legs were improved.

Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease / 华中科技大学学报（医学）（英德文版）

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-1-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, thrombocytopenia, 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. Improved or recovered liver function 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 period 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 maintain lifelong therapy.

Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents (Icap). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on Icap. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on Icap. The PKG inhibitor KT5823 prevented the inhibition of Icap by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

Wilson's disease in southern Brazil: a 40-year follow-up study

BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5 percent had a European ancestor. The mean age at the initial symptom presentation was 23.3 ± 9.3 years, with a delay of 27.5 ± 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9 percent), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6 percent) and neuropsychiatric symptoms (25 percent). Kayser-Fleischer rings were identified in 55.6 percent of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8 percent). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2 percent of these patients. Chronic liver disease was detected in 68 percent of the patients with hepatic symptoms. 94.2 percent of all the patients were treated with D-penicillamine for a mean time of 129.9 ± 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8 percent of the patients had a stable or improved outcome, and the overall survival rate was 90.1 percent. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.

Comparative study of the role of D- pencillamine and garlic extract in treatment of lead poisoning in adult albino rats

Lead is one of the most useful materials in the world. The aim of this study was to compare the curative role of D-penicillamine and garlic extract in treatment of lead poisoning in adult albino rats. The study included 80 adult albino rats consisted of 7 groups. The period of lead intoxication extended for 3 months followed by either 1 month treatment [penicillamine or garlic extract] or 1 month of no treatment. Group I: consisted of 20 rats divided equally into the negative and positive control subgroups. Each of groups 11- VII consisted into 10 rats. Group [I: [P] Pencillamine alone in a dose of 25 mg/kg 6 days/ week for 1 month. Group III: [G] garlic extract alone in a dose of 20 mg/kg 6 days/ wk for I month. Group IV: [Pb] lead poisoning in a dose of 20 mg/kg 6 days/ wk for 3 months. Group V: [Pb-P] treatment with penicillamine in Pb poisoning. Group VI: [Pb-G] treatment with garlic extract in Pb poisoning. Group VII: [Pb-F] follow up of Pb poisoning without treatment. The results of this study revealed that lead poisoning significantly elevated blood lead level [BLL] and testicular lead level [TLL] when compared with the negative control rats. Lead was testicular toxicant as it produced atrophic germinal epithelium and arrested spermatogenesis. Treatment of Pb poisoning by penicillamine or garlic extract resulted in significant decrease in BLL and TLL with significant increase in urinary lead level [ULL] when compared with the Pb treated rats. Also, P and G treatment resulted in improvement of testicular structure. [n follow up group, BLL, ULL and TLL were significantly increased when compared with the negative control rats. Also, BLL was significantly decreased when compared with lead treated group. There was minimal improvement in testicular structure in Pb-F group. It was concluded that both penicillamine and garlic can treat lead poisoning. Moreover, garlic curative effect is better than that of penicillamine. garlic can be considered as a chelating agent in treatment of lead poisoning