Arylamines QSAR-Based Design and Molecular Dynamics of New Phenylthiophene and Benzimidazole Derivatives with Affinity for the C111, Y268, and H73 Sites of SARS-CoV-2 PLpro Enzyme.

A non-structural SARS-CoV-2 protein, PLpro, is involved in post-translational modifications in cells, allowing the evasion of antiviral immune response mechanisms. In this study, potential PLpro inhibitory drugs were designed using QSAR, molecular docking, and molecular dynamics. A combined QSAR equation with physicochemical and Free-Wilson descriptors was formulated. The r2, q2, and r2test values were 0.833, 0.770, and 0.721, respectively. From the equation, it was found that the presence of an aromatic ring and a basic nitrogen atom is crucial for obtaining good antiviral activity. Then, a series of structures for the binding sites of C111, Y268, and H73 of PLpro were created. The best compounds were found to exhibit pIC50 values of 9.124 and docking scoring values of -14 kcal/mol. The stability of the compounds in the cavities was confirmed by molecular dynamics studies. A high number of stable contacts and good interactions over time were exhibited by the aryl-thiophenes Pred14 and Pred15, making them potential antiviral candidates.

Design, Synthesis, and Structure-Activity Relationship Studies of New Quinone Derivatives as Antibacterial Agents.

Resistance to antibacterial agents is a growing global public health problem that reduces the efficacy of available antibacterial agents, leading to increased patient mortality and morbidity. Unfortunately, only 16 antibacterial drugs have been approved by the FDA in the last 10 years, so it is necessary to develop new agents with novel chemical structures and/or mechanisms of action. In response to this, our group takes up the challenge of designing a new family of pyrimidoisoquinolinquinones displaying antimicrobial activities against multidrug-resistant Gram-positive bacteria. Accordingly, the objective of this study was to establish the necessary structural requirements to obtain compounds with high antibacterial activity, along with the parameters controlling antibacterial activity. To achieve this goal, we designed a family of compounds using different strategies for drug design. Forty structural candidates were synthesized and characterized, and antibacterial assays were carried out against high-priority bacterial pathogens. A variety of structural properties were modified, such as hydrophobicity and chain length of functional groups attached to specific carbon positions of the quinone core. All the synthesized compounds inhibited Gram-positive pathogens in concentrations ranging from 0.5 to 64 µg/mL. Two derivatives exhibited minimum inhibitory concentrations of 64 µg/mL against Klebsiella pneumoniae, while compound 28 demonstrated higher potency against MRSA than vancomycin.

First report of Wilson disease and Bruton agammaglobulinemia in the same patient caused by new mutations in ATP7B and BTK genes.

INTRODUCTION: Wilson disease is characterized by an alteration in copper metabolism that causes its accumulation in different tissues. Its diagnosis is established by the combination of clinical manifestations and paraclinical and genetic studies. Bruton agammaglobulinemia is an X-linked recessive hereditary disease belonging to the group of primary immunodeficiencies and is produced by mutation in the Bruton tyrosine kinase (BTK) gene. CASE REPORT: A 14-year-old Colombian patient with clinical characteristics of Bruton agammaglobulinemia presented with liver disease and clinically and molecularly diagnosed with Wilson disease. DISCUSSION: Bruton agammaglobulinemia and Wilson disease are considered rare diseases because of their low prevalence. We report for the first time a pediatric patient from southwestern Colombia presenting with both entities, and diagnosed clinically and molecularly, an association so far not reported in the literature.

A Custom-Made Newborn Screening Test for Wilson's Disease in Puerto Rico.

Background Wilson's disease (WD) is an autosomal recessive progressive, disabling, life-threatening disease. Although early diagnosis and treatment can halt disease progression and reverse disability, diagnosis is often challenging, with a mean diagnostic delay of approximately two years. At least 98% of WD-causing variants are in the ATPase copper transporting beta (ATP7B) gene. Identifying ATP7B mutations that cause WD in Puerto Rico will allow newborn screening for WD, as well as preventive, life-saving treatment. Methodology TaqMan genotyping assays were performed on 174 random volunteers in southwestern Puerto Rico and on three independent WD cases for rs367956522 and rs140708492, single-nucleotide polymorphisms (SNPs) composing a WD-causing haplotype. A polymerase chain reaction followed by Sanger DNA sequencing confirmed the case genotypes. Bioinformatics analyses were performed on ATP7B polymorphisms present in The 1000 Genomes Project (1KGP) database for Puerto Rico. Results rs367956522 is always inherited together with rs140708492 but not vice versa. The three independent WD cases were homozygous for both SNPs, but the evidence strongly suggested that rs367956522 is the pathogenic variant. The 1KGP database revealed the presence of only one other likely pathogenic ATP7B variant, rs191312027 (Gly869Arg). Together, both variants may be responsible for causing WD in one of every 14,156 Puerto Ricans. Both are likely of European origin. Conclusions Genotyping probes for both variants are readily commercially available. Thus, rapid, inexpensive newborn screening for rs367956522 and rs191312027 is strongly recommended. Although these two variants may account for all or the vast majority of WD cases in Puerto Rico, other ATP7B polymorphisms described or not described in this study might also be pathogenic.

New ATP7B Gene Mutation in a Brazilian Patient with Wilson Disease.

We report the case of a 70-year-old man diagnosed with late-onset Wilson disease (WD) with mild neurological symptoms only and a new mutation in the ATP7B gene. A compound mutation of the ATP7B gene was found with the variant c.98T>C p(Met33Thr) in exon 2, in heterozygosis, and variant c.2224G>A (Val742Ile) in exon 8, in heterozygosis. Patient age should not be a determinant for excluding WD. Genetic sequencing is an important tool for the discovery of new genetic mutations. LEARNING POINTS: Wilson disease (WD) is an autosomal recessive disorder of copper metabolismPatient age should not exclude WD, and symptoms compatible with WD should raise suspicion for WD even in older people.Genetic sequencing is an important tool in the discovery of new genetic mutations.

Solubility of Sulfamethazine in the Binary Mixture of Acetonitrile + Methanol from 278.15 to 318.15 K: Measurement, Dissolution Thermodynamics, Preferential Solvation, and Correlation.

Solubility of sulfamethazine (SMT) in acetonitrile (MeCN) + methanol (MeOH) cosolvents was determined at nine temperatures between 278.15 and 318.15 K. From the solubility data expressed in molar fraction, the thermodynamic functions of solution, transfer and mixing were calculated using the Gibbs and van 't Hoff equations; on the other hand, the solubility data were modeled according to the Wilson models and NRTL. The solubility of SMT is thermo-dependent and is influenced by the solubility parameter of the cosolvent mixtures. In this case, the maximum solubility was achieved in the cosolvent mixture w0.40 at 318.15 K and the minimum in pure MeOH at 278.15 K. According to the thermodynamic functions, the SMT solution process is endothermic in addition to being favored by the entropic factor, and as for the preferential solvation parameter, SMT tends to be preferentially solvated by MeOH in all cosolvent systems; however, δx3,1<0.01, so the results are not conclusive. Finally, according to mean relative deviations (MRD%), the two models could be very useful tools for calculating the solubility of SMT in cosolvent mixtures and temperatures different from those reported in this research.

Digital restoration of the Wilson-Leonard 2 Paleoindian skull (~10,000 BP) from central Texas with comparison to other early American and modern crania.

OBJECTIVES: Craniofacial morphology (CFM) is often used to address questions about the biological affinities of the earliest Americans, or Paleoindians, but resolution is complicated in part by a lack of well-preserved crania. The Wilson-Leonard 2 (WL-2) Paleoindian skull from Texas has never been fully analyzed because it is crushed and cannot be physically reconstructed. This study employs a digital restoration for comprehensive assessment and analysis of WL-2. MATERIALS AND METHODS: High-resolution CT data and geometric morphometrics are used to restore the WL-2 skull and analyze its morphology using 65 craniometric measurements acquired on the restoration. These data allow for a full morphological description and multivariate (Mahalanobis Distance and Principal Component) comparisons to other Paleoindians and recent populations. RESULTS: WL-2 has a long, narrow braincase, and a short, modestly prognathic face. Compared with other Paleoindians, she is individually similar to several skulls from Brazil, but aligns most closely with pooled samples from the US and Mexico. WL-2 is most similar to recent populations from Europe, Asia, and the Americas, and markedly different to those from Africa and Australia. DISCUSSION: The overall morphology of WL-2 and her association with Asians and Europeans align well with trends identified in other CFM analyses. Her affinity to recent Amerindians contrasts with the findings of many previous CFM studies, but is seemingly consistent with molecular analyses suggesting a close relationship between some Paleoindians and modern American Indians. This study demonstrates the potential for using digital anthropological methods to study other Paleoindian crania whose data value is limited by physical destruction and/or deformation.

Characteristics and outcomes of hospitalized patients with Wilson's disease in the United States: A national survey.

INTRODUCTION AND OBJECTIVES: Wilson's disease (WD) is a rare genetic disorder characterized by excessive copper disposition predominantly in the liver and brain. Hospitalization data on patients with WD are scarce. Hence, we sought to examine the inpatient characteristics and outcomes of patients with WD. PATIENTS AND METHODS: We utilized the National Inpatient Database (2006-2011) and analyzed all adult patients with a diagnosis of WD. RESULTS: There were 9046 hospitalizations during the study period. The leading etiologies for admissions were chronic liver disease (8.58%), WD (6.49%) and infections (septicemia 3.10% and pneumonia 2.50%). The overall inpatient mortality rate for WD patients was 2.58%. Independent predictors of mortality in WD patients were acute respiratory failure (OR: 4.53; 95% CI: 2.44-8.42), acute renal failure (OR: 4.09; 95% CI: 2.19-7.65), decompensated liver disease or liver failure (OR: 3.37; 95% CI: 1.72-6.59), and advanced age (every 10 year increase, OR: 1.48; 95% CI: 1.25-1.75). Propensity-score matched analysis revealed better inpatient survival in WD patients compared to matched non-WD patients (2.84% vs. 4.67%, p = 0.01). CONCLUSIONS: Our study demonstrated the clinical characteristics and outcomes of hospitalized patients with WD. These findings add important knowledge to our understanding of the healthcare utilization and outcomes of this rare disease in the United States.

Osmotic demyelination syndrome diagnosed radiologically during Wilson's disease investigation.

Wilson's disease (WD), also known as hepatolenticular degeneration, is a rare autosomal recessive disorder that results from abnormal ceruloplasmin metabolism, with copper deposition affecting multiple systems. Osmotic demyelination syndrome (ODS) refers to acute demyelination seen in the setting of osmotic changes, typically with the rapid correction of electrolyte disturbance. We present a 29-year-old male patient diagnosed with WD 1 year after the onset of extrapyramidal symptoms. Magnetic resonance imaging performed during hospitalization showed two patterns of pons involvement, which allowed the diagnosis of ODS in addition to WD. Classic imaging findings were observed and illustrate perfectly these two conditions.

Avaliação do Escore de Wilson e do Teste de Mallampati modificado como preditores de difícil intubação orotraqueal: Estudo transversal / Evaluation of the Wilson risk-sum and the modified Mallampati Test as predictors of difficult orotracheal intubation: Cross-sectional study

INTRODUÇÃO: A consulta pré-anestésica é de extrema importância para o médico anestesiologista no planejamento do manejo das vias aéreas de pacientes sob o efeito de anestesia geral com intubação orotraqueal (IOT). OBJETIVO: Avaliar a sensibilidade, especificidade, valor preditivo positivo/negativo (VPP/VPN) de testes de predição de IOT difícil (Escore de Wilson - EW, e Teste de Mallampati modificado - TMM), em pacientes submetidos à anestesia geral, em hospital filantrópico do interior de Minas Gerais. MATERIAIS E MÉTODOS: Estudo descritivo transversal, por meio de fichas pré-anestésicas e transoperatórias, de pacientes submetidos à anestesia geral com IOT, entre os meses de janeiro (2019) e março (2020). RESULTADOS: Dos 440 pacientes, 56,1% necessitaram de IOT: média de idade de 49,9 anos (desvio padrão 18,6). A maioria foi classificada: TMM classe I e II; pontuação 0 a 2 no EW; distância esternomentoniana >12,5 cm, sugerindo IOT fácil. Apenas o TMM apresentou correlação com IOT difícil (p=0,045). Sensibilidade e especificidade dos testes respectivamente: TMM (54,6%;75,9%); EW (36,4% e 79,7%); baixo VPP (TMM: 9,5%; EW: 7,7%) e alto VPN (TMM: 97,3%; EW: 96,4%). Curva ROC: área sob a curva foi de TMM = 0,68; EW = 0,60. CONCLUSÃO: Apesar do TMM apresentar correlação significativa com a IOT difícil, não foi possível definir o melhor teste preditor. Ressaltamos que a sensibilidade e o VPP, de ambas as avaliações, ficaram abaixo daquilo que seria considerado adequado para um teste de rastreio e predição.

Introduction: A pre-anesthetic appointment is extremely important for the anesthesiologist when planning the management of the airways of patients under the effect of general anesthesia with orotracheal intubation (OTI). Objective: To evaluate the sensitivity, specificity, positive/ negative predictive value (PPV/NPV) of difficult OTI prediction tests (Wilson risk-sum ­ WRS, and Modified Mallampati Test - MMT) in patients undergoing general anesthesia in a philanthropic hospital in the countryside of the state of Minas Gerais. Materials and methods: Descriptive cross-sectional study using pre-anesthetic and transoperative records of patients submitted to general anesthesia with OTI between the months of January (2019) and March (2020). Results: Of the 440 patients, 56.1% required OTI: average age of 49.9 years (standard deviation 18.6). Most classified: MMT class I and II; score 0 to 2 on the WRS; sternomental distance greater than 12.5 cm, suggesting easy OTI. Only MMT showed statistical significance with difficult OTI (p=0.045). Sensitivity and specificity of the tests respectively: MMT (54.6%; 75.9%) WRS (36.4% and 79.7%) low PPV (MMT: 9.5%; WRS: 7.7%) and high NPV (MMT: 97.3%; WRS: 96.4%). ROC Curve: area under the curve was MMT = 0,68; WRS = 0,60. Conclusion: Although the MMT has a significant correlation with the difficult OTI, it was not possible to define the best predictor test. We emphasize that the sensitivity and PPV of both evaluations were below what would be considered adequate for a screening and prediction test.

Considerações odontológicas no atendimento ao paciente com doença de Wilson: relato de caso / Dental considerations in the care of the patient with Wilson disease: case report

A Doença de Wilson é uma doença autossômica recessiva que ocasiona no individuo metabolismo deficiente de cobre pelo fígado, compromete as funções hepática e neurológicas, a moléstia evolui de forma progressiva tornando-se potencialmente fatal, caso não seja diagnosticada precocemente e seu tratamento instituído. O presente artigo relata um caso clinico de uma paciente do gênero feminino, melanoderma, 33 anos, diagnosticada com Doença de Wilson-(DW), desde então acompanhada pela equipe multiprofissional durante seu período de hospitalização, em que ocorreu atuação da Odontologia hospitalar nas manifestações clinicas bucais, contribuindo com a adequação do meio bucal através de exames radiográficos e procedimentos realizados no leito. A Odontologia contribuiu com abordagem clínica, intervenção em leito, exames radiográficos, controle de biofilme, possibilitando adequação do meio bucal e melhora do quadro de sangramento gengival. Dessa forma a odontologia se fez presente realizando procedimentos que contribuem na melhora do quadro sistêmico, assim como sendo as "mãos de quem já não possui a autonomia" de realizar atividades básicas como a higiene bucal. Ainda existe um longo caminho de pesquisas e estudos para que o diagnóstico diferencial da DW possa ser realizado de forma mais rápida, visto que se assemelha a outras patologias(AU)

Wilson's disease needs to be better understood, thus reinforcing the need for a precancer diagnosis. Regarding the impairment of the oral cavity due to the evolution of DW, it is well known that the patients affected by this disease receive a dental follow-up, since many are totally dependent on self-care and may cause the individual with DW unsatisfactory oral conditions with repercussion in its systemic picture(AU)

Wilson disease in Costa Rica: Pediatric phenotype and genotype characterization.

INTRODUCTION: The prevalence of Wilson disease (WD) in Costa Rica is among the highest reported in the world, 4.9:100 000. Previous investigators have also described a burden of autosomal recessive conditions in this country. Genetic testing for WD began in 2010 as a strategy for earlier detection due to the country's high prevalence. Here we describe what we have learned about the genotype and phenotype of the Costa Rican pediatric population with WD. METHODS: We completed a retrospective review of medical records from pediatric individuals (<18 years of age) with molecular testing for ATP7B between 2010 and 2015. We documented phenotype and genotype for cases with WD as defined by the international scoring system. RESULTS: Thirty-four WD cases from 28 families were included, 15 female and 19 male patients. The most frequent pathogenic variant in ATP7B was NM_000053:c.3809A>G, p.Asn1270Ser, with 58.8% of affected individuals homozygous for this variant. Age of diagnosis ranged from 1 to 17 years, with an average of 8.8 ± 3.6 years. All individuals who presented with acute liver failure (n = 6) were homozygous for the p.Asn1270Ser variant (Chi-squared, P < .05). DISCUSSION: Molecular testing has facilitated the detection of presymptomatic patients with WD in Costa Rica. We hope that ongoing efforts in the delivery of clinical services lead to optimized molecular screening for WD and other genetic conditions in Costa Rica.

Brain oxidative stress in rat with chronic iron or copper overload.

Male rats of 80-90 g that were fed 42 days with a commercial rodent diet of 2780 kcal/100 g and received chronic overloads of either Fe(II) or Cu(II) in the drinking water. The two metals produced brain oxidative stress and damage with marked increases in the indicators of oxidative processes: in vivo brain surface chemiluminescence (the sensitive organ non-invasive assay for oxidative free radical reactions), and the ex vivo processes of phospholipid peroxidation and protein oxidation. Brain redox imbalance was also indicated by marked decreases in the cellular indicators of oxidative metabolic stress: reduced glutathione (GSH) content and reduced/oxidized glutathione ratio (GSH/GSSG). Brain decreased GSH content has a central role in the biochemical oxidative processes associated with Fe and Cu chronic damage. The understanding of biochemical oxidative imbalances in the rat brain with chronic Fe(II) or Cu(II) overloads may be useful for the establishment of pharmacological therapies for human pathologies associated to Fe and Cu cellular imbalances.

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.

Plasma transfusion combined with chelating therapy alleviates fulminant Wilson's disease with a single Arg778Leu heterozygote mutation.

Wilson's disease (WD), resulting from homozygote and compound heterozygote mutations in ATB7B, is an autosomal recessive disease. WD associated acute liver failure (ALF) is fatal, and a revised Wilson's disease prognostic index (RWPI) >11 is a reliable indication of liver transplantation (LT) or artificial liver support (ALS). We described a WD patient who initially presented with ALF and severe hemolytic anemia. A single heterozygote c.2333G>T mutation (p. Arg778Leu, R778L) in ATP7B was screened by whole exome sequencing and validated by Sanger sequencing. Rapid diagnostic criteria (ALP/TBIL <4 and AST/ALT >2.2) are suitable for early diagnosis. Although the RWPI amounted to 15, the patient recovered after intermittent plasma transfusion and subsequent chelating therapy without LT or ALS. In conclusion, WD patients with a single R778L heterozygote mutation can present with ALF as the initial clinical manifestation, and intermittent plasma transfusion combined with chelating therapy may alleviate fulminant WD without LT or ALS.

[Wilson disease: The look of medical staff, patients and family members]. / La enfermedad de Wilson: las diversas perspectivas del profesional sanitario, afectado y familiar.

OBJECTIVE: Wilson disease (WD) is a rare congenital disease that causes hepatic, neurological or lenticular degeneration due to the accumulation of copper. Sometimes it is incapacitating with implications in the quality of life of those affected and their families. The objective of this work was to identify the needs of medical staff and the social and emotional needs of patients with WD and their families. METHODS: A qualitative research was developed in the Valencian Region during 2015-2016, five interviews with medical staff and two focus groups were made, one with family members and another with patients using a script divided into: diagnosis, treatment, health care and quality of life. The information was collected in audio/video and transcribed. An analysis of discourse (professional vs family/affected) determining needs was made. RESULTS: Medical staff need more knowledge about this pathology. Better educational training for them would facilitate the diagnosis. Families and patients need more information about the guidelines for the treatment's administration and foods that should be excluded from the diet. The correct administration of the treatment will allow those affected to improve their quality of life with a total or partial recovery of their symptoms.. CONCLUSIONS: Peru has made significant progress in reducing chronic malnutrition in children, but it still represents a health problem due to high prevalence in the sierra and expansion to jungles districts in 2016. Policies and programs should continue and enhance to avoid the high burden of disease that generates malnutrition in the development of children.

OBJETIVO: La Enfermedad de Wilson (EW) es una patología rara congénita y hereditaria que se produce por acumulación de cobre en el organismo, degeneración crónica hepática, neurológica o lenticular. En ocasiones es incapacitante por lo que influye en la calidad de vida de afectados y familiares. El objetivo de este trabajo fue identificar las necesidades médicas, sociales y emocionales de pacientes y familiares. METODOS: Con metodología cualitativa se realizaron en la Comunitat Valenciana (CV), en 2015-2016, 5 entrevistas a profesionales sanitarios y 2 grupos de discusión, uno con familiares y otro con afectados. Se elaboró un guión estructurado en: diagnóstico, tratamiento, atención sanitaria y calidad de vida. La información se recogió en audio/video, previa autorización y se transcribió literalmente. Se realizó un análisis del discurso (profesionales vs. familiares/afectados) determinando necesidades y demandas concretas. RESULTADOS: Los profesionales se mostraron emocionalmente distantes de las necesidades emocionales de afectados y familiares y consideraron necesario disponer de mayor información para facilitar el diagnóstico precoz. Las familias expresaron preocupación sobre la adherencia al tratamiento, especialmente en adolescentes, y confusión sobre la importancia de seguir una dieta baja en cobre. Los afectados reconocieron tener dudas sobre la funcionalidad de la medicación. Los afectados neurológicamente se sintieron estigmatizados por las secuelas físicas de la enfermedad. CONCLUSIONES: Los sanitarios consideran que tener un mayor conocimiento sobre esta enfermedad facilitaría una detección precoz. Familiares y afectados necesitan indicaciones claras y especificadas sobre las pautas de administración del tratamiento y sobre los alimentos que deben excluir de la dieta.

Redox dyshomeostasis in the experimental chronic hepatic overloads with iron or copper.

Male rats of 80-90 g were overloaded with either Fe(II) or Cu(II) for 42 days by high concentrations of FeCl2 or CuSO4 in the drinking water. The animals were fed with a commercial rodent diet of 2780 kcal/100 g. Both metal treatments led to a liver redox imbalance and dyshomeostasis with oxidative stress and damage and the concomitant enhancement of oxidative processes as indicated by in vivo surface liver chemiluminescence, the sensitive and organ non-invasive assay for oxidative free radical reactions, and by ex vivo determined processes of phospholipid peroxidation and protein oxidation. In parallel, marked decreases in the antioxidant defense were observed. Liver reduced glutathione (GSH) content and the reduced/oxidized glutathione ratio (GSH/GSSG) were early indicators of oxidative metabolic disturbance upon the metal overloads. Thus, GSH plays a central role in the defense reactions involved in the chronic toxicity of Fe and Cu. Chronic overloads of Fe or Cu in rats afford an experimental animal model of hemochromatosis and of Wilson's disease, respectively. These two animal models could be useful in the study and development of the beneficial effects of pharmacological interventions in the two human diseases.