Characterisation of UDP-glucuronosyltransferase activity in sea turtle Chelonia mydas.

Uridine diphosphate glucuronosyltransferase (UGT) enzymes conjugate many lipophilic chemicals, such as drugs, environmental contaminants, and endogenous compounds, promoting their excretion. The complexity of UGT kinetics, and the location of enzyme active site in endoplasmic reticulum lumen, requires an accurate optimisation of enzyme assays.In the present study, we characterised UGT activity in liver microsomes of green turtles (Chelonia mydas), an endangered species. The conditions for measuring UGT activity were standardised through spectrofluorimetric methods, using the substrates 4-methylumbelliferone (4-MU) and uridine diphosphate glucuronic acid (UDPGA) at 30 °C and pH 7.4.The green turtles showed UGT activity at the saturating concentrations of substrates of 250 µM to 4-MU and 7 mM to UDPGA. The alamethicin, Brij®58, bovine serum albumin (BSA), and magnesium increased UGT activity. The assay using alamethicin (22 µg per mg of protein), magnesium (1 mM), and BSA (0.25%) reached the highest Vmax (1203 pmol·min-1mg·protein-1). Lithocholic acid and diclofenac inhibited UGT activity in green turtles.This study is the first report of UGT activity in the liver of green turtles and provides a base for future studies to understand the mechanisms of toxicity by exposure to contaminants in this charismatic species.

Incidence of falls and preventive actions in a University Hospital. / Incidência de quedas e ações preventivas em um Hospital Universitário.

Objective Describing the incidence of falls and its relation with preventive actions developed in a Brazilian university hospital. Method A retrospective longitudinal study. Hospitalized adult patients in the clinical, surgical, psychiatric and emergency units who suffered a fall in the institution, and who had the event notified in the period from January 2011 to December 2015 were included in the study. The data were collected from the institution's management information system and analyzed in the SPSS statistical program. Results There were 2,296 falls, with a mean incidence of 1.70 falls/1,000 patients per day. An increase in the incidence of falls was observed in the period from 2011 (1.61) to 2012 (2.03). In the following years, the incidence of falls decreased from 1.83 falls/1,000 patients per day in 2013 to 1.42 falls/1,000 patients per day in 2015. The incidence of falls accompanied an implementation of preventive actions, suggesting the impact of such interventions in reducing the event occurrence. Conclusion The findings demonstrate the importance of implementing preventive interventions in reducing the incidence of falls in hospitalized patients.

Biochemical responses in Pacific oysters Magallana gigas (Thunberg, 1793): Tools to evaluate the environmental quality of aquaculture areas.

The discharge of sanitary sewage into the bays of the Florianópolis Metropolitan Area (Southern Brazil), has led to the contamination of oyster farms. Consequently, linear alkylbenzenes (LABs) were quantified in the sediment, and the biochemical responses in gills and digestive gland of oysters from six farms were assessed. Our findings revealed elevated levels of LABs in the sediment of the Imaruim and Serraria farms. Additionally, alterations were observed in the antioxidant enzymes: catalase, glutathione peroxidase and superoxide dismutase in both oyster tissue from the Serraria, Santo Antonio de Lisboa and Sambaqui farms. Furthermore, correlation analyses indicated strong and moderate associations between biochemical responses, organic contaminants, and certain physicochemical parameters. Consequently, our results demonstrated the activation of the antioxidant system in oysters, representing a protective response to the presence of sanitary sewage and other contaminants. Therefore, we propose the utilization of biochemical biomarkers for monitoring the environmental quality of farms.

Emerging and legacy contaminants on the Brazilian southern coast (Santa Catarina): A multi-biomarker approach in oysters Crassostrea gasar (Adanson, 1757).

Coastal environments, such as those in the Santa Catarina State (SC, Brazil), are considered the primary receptors of anthropogenic pollutants. In this study, our objective was to evaluate the levels of emerging contaminants (ECs) and persistent organic pollutants (POPs) in indigenous Crassostrea gasar oysters from different regions of SC coast in the summer season (March 2022). Field collections were conducted in the São Francisco do Sul, Itajaí, Florianópolis and Laguna coastal zones. We analyzed the bioaccumulation levels of 75 compounds, including antibiotics (AB), endocrine disruptors (ED), non-steroidal anti-inflammatory drugs (NSAIDs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and pesticides. Furthermore, we assessed biomarker responses related to biotransformation, antioxidant defense, heat shock protection and oxidative damage in oysters' gills. Prevalence of ECs was observed in the central and southern regions, while the highest concentrations of POPs were detected in the central-northern regions of SC. Oysters exhibited an induction in biotransformation systems (cyp2au1 and cyp356a1, sult and GST activity) and antioxidant enzymes activities (SOD, CAT and GPx). Higher susceptibility to lipid peroxidation was observed in the animals from Florianópolis compared to other regions. Correlation analyses indicated possible associations between contaminants and environmental variables in the biomarker responses, serving as a warning related to climate change. Our results highlight the influence of anthropogenic activities on SC, serving as baseline of ECs and POPs levels in the coastal areas of Santa Catarina, indicating more critical zones for extensive monitoring, aiming to conserve coastal regions.

Comparative biochemical and molecular responses of biotransformation and antioxidant systems in three species of Crassostrea (Sacco, 1897) oysters exposed to chrysene.

Chrysene (CHR) is among the most persistent polycyclic aromatic hydrocarbons (PAH) in water and a priority compound for pollutants monitoring, due to its carcinogenic, mutagenic and genotoxic potential. Aquatic animals exposed to CHR may present alterations of biomarkers involved in the biotransformation and oxidative stress-related parameters. The aim of this study was to investigate differences in antioxidant and biotransformation (phase I and II) systems of Crassostrea gigas, C. gasar and C. rhizophorae and its effects resulting from CHR exposure. Adult oysters of these species were exposed to 10 µg L-1 of CHR for 24 h and 96 h. In gills, the transcripts CYP1-like, CYP2-like, CYP2AU1-like, GSTO-like, MGST-like, SULT-like were evaluated after 24 h of exposure. The activity of SOD, CAT, GPx, GR and G6PDH were analyzed in gills and digestive glands after 96 h of exposure. CHR bioaccumulated in tissues. Differences in the remaining levels of CHR in water after 96 h were observed in aquaria containing C. gigas or C. gasar oysters and may be associated to the different filtration rates between these species. Downregulate of biotransformation genes were observed in gills of C. gasar (CYP2AU1-like and GSTO-like) and C. rhizophorae (CYP1-like1, CYP2-like, MGST-like and SULT-like), suggesting that biotransformation responses may be species-specific. Differential activity of antioxidant enzymes were observed in gills and digestive gland of oysters exposed to CHR. Biochemical responses suggested that C. gigas and C. gasar are more responsive to CHR. Differential responses observed among the three Crassostrea species can be related to evolutionary differences, ecological niches and adaptation to environment.

[Formula: see text]Socioeconomic aspects are crucial to better intellectual outcome in early-treated adolescents with congenital hypothyroidism.

Congenital hypothyroidism (CH) is an important cause of preventable intellectual disability. Implementation of CH neonatal screening programs leading to early treatment has improved cognitive outcome. However, more subtle cognitive impairments are still reported, and there is lack of clarity regarding factors that impact long-term cognitive outcome. Research to better understand these factors can lead to further improvements in the cognitive prognosis for these patients. The current study aimed to evaluate the cognitive performance of adolescents who were early-treated for primary permanent CH and possible associated variables. Neurocognitive evaluation was carried out in 66 adolescents, 11 to 16 years old: 34 with CH and 29 paired controls. Intellectual quotient (IQ), verbal fluency, processing speed, executive functions, and memory were investigated. CH patients and control subjects were comparable regarding sex, age, schooling, family's socioeconomic status and caregiver's educational level. Both groups presented not only similar IQ scores but also equivalent performances regarding Perceptual Reasoning, Working Memory and Processing Speed index scores. Patients presenting different CH etiologies (dysgenesis and dyshormonogenesis) showed similar cognitive performance. Socioeconomic aspects along with the initial levothyroxine dose were the main variables to positively influence the cognitive performance, the family's socioeconomic status having the strongest association with patients' cognitive skills.

Hepcidin messenger RNA expression in human lymphocytes.

Hepcidin regulates intracellular iron levels by interacting with and promoting the degradation of ferroportin, a membrane protein and the only known cellular iron exporter. Studies of hepcidin expression and regulation have focused on its effects in innate immunity and as a regulator of systemic iron metabolism. In the present study we characterized the expression of hepcidin messenger RNA (mRNA) in human peripheral blood mononuclear cells (PBMCs) with a focus on peripheral blood lymphocytes (PBLs). We found that (1) all human PBMCs analyzed express basal hepcidin mRNA levels; (2) hepcidin mRNA expression increases after T-lymphocyte activation; (3) expression by PBLs increases in response to challenge by holotransferrin (Fe-TF) and by ferric citrate in vitro; (4) the Fe-TF-mediated up-regulation of hepcidin decreases ferroportin expression at the cytoplasmic membrane of PBLs; and (5) silencing of tumour necrosis factor-alpha (TNF-alpha) abrogates the effect of Fe-TF. In summary, we show that hepcidin expression determines intracellular iron levels by regulating the expression of ferroportin, as described in other cells, and that inappropriately low expression of hepcidin impairs normal lymphocyte proliferation. The results establish hepcidin as a new player in lymphocyte biology.

Translation and Validation of the Patient Activation Measure in Portuguese People with Type 2 Diabetes Mellitus.

INTRODUCTION: Management of diabetes mellitus is largely dependent on patients' active participation in care. The 'Patient Activation Measure 13' assesses patients' knowledge, skills, and confidence in self-care. We aimed to translate, culturally adapt, and validate the 'Patient Activation Measure 13' to Portuguese, in people with type 2 diabetes. MATERIAL AND METHODS: The translation and cultural adaptation occurred in six phases. A convenience sample of people with type 2 diabetes was recruited from the waiting rooms of a diabetes outpatient centre in Lisbon, between March and April 2014. The questionnaire was self-administered; medical records were reviewed to obtain glycated haemoglobin levels. Main statistical analyses were based on the Rasch rating scale model. RESULTS: The response rate for the final questionnaire was 76%. Rasch analysis was conducted on 193 respondents. Respondents had a mean age of 67.1 (SD 10.1) years, 42.7% were women, and the mean patient activation measure score (0 - 100) in the sample was 58.5 (SD 10.1). The sample was low to moderate in terms of activation: 40.4% were low in activation (levels 1 and 2), 49.7% were in level 3, and 9.8% were in level 4, the highest level of activation. All items had good fit and the response categories functioned well. Item reliability was 0.97 and person reliability was between 0.77 (real) and 0.83 (model). DISCUSSION: The 'Patient Activation Measure 13' was translated and culturally adapted to European Portuguese and validated in people with diabetes, showing good psychometric properties. Future research should aim at evaluating test-retest reliability of the Portuguese 'Patient Activation Measure 13', and exploring its ability to measure changes in activation over time. CONCLUSION: The 'Patient Activation Measure 13' is now available in European Portuguese and has good psychometric properties.

Introdução: A gestão da diabetes mellitus é, em grande parte, dependente da participação ativa dos doentes no processo de cuidados. O questionário de ativação do doente (Patient Activation Measure 13) avalia o conhecimento, capacidade técnica e confiança do doente nos auto-cuidados. Este estudo teve como objetivo a tradução, adaptação cultural e validação do questionário Patient Activation Measure 13 para português, em pessoas com diabetes tipo 2. Material e Métodos: A tradução e adaptação cultural ocorreu em seis fases. O recrutamento decorreu nas salas de espera da Associação Protetora dos Diabéticos de Portugal, entre março e abril de 2014 (amostra de conveniência). O questionário foi auto- administrado; os valores de hemoglobina glicada foram obtidos a partir do processo clínico eletrónico. A análise psicométrica baseou- se no modelo de Rasch. Resultados: A taxa de resposta foi de 76% e 193 indivíduos foram incluídos na análise psicométrica. A idade média dos participantes foi 67 (desvio padrão 10,1) anos, 42,7% eram mulheres, e a média do score do Patient Activation Measure (0 - 100) na amostra foi 58,5 (desvio padrão 10,1). A amostra apresentou níveis baixos a moderados de ativação. Todos os itens apresentaram bom ajuste e as categorias de resposta funcionaram adequadamente. A fiabilidade dos itens foi 0,97 e a fiabilidade das pessoas encontrou-se entre 0,77 (real) e 0,83 (modelo). Discussão: O Patient Activation Measure 13 foi traduzido e adaptado culturalmente para português, bem como validado em pessoas com diabetes mellitus tipo 2, revelando boas propriedades psicométricas. Estudos futuros deverão avaliar a fiabilidade teste-reteste do Patient Activation Measure 13 Português e explorar a capacidade do mesmo em avaliar alterações na ativação ao longo do tempo. Conclusão: O Patient Activation Measure 13 está agora disponível para utilização na população Portuguesa, apresentando boas propriedades psicométricas.

The expression of the solute carriers NTCP and OCT-1 is regulated by cholesterol in HepG2 cells.

Drug disposition and response are greatly determined by the activities of drug-metabolizing enzymes and transporters. While the knowledge in terms of CYP enzymes and efflux ABC transporters (such as MDR1, P-glycoprotein) is quite extensive, influx transporters are increasingly being unveiled as key contributors to the process of drug disposition. There is little information on the regulation of these proteins in human cells, especially as regards the effect of endogenous compounds. In this study, we analysed the expression of CYP3A4 and three uptake transporters NTCP (SLC10A1), OATP-A/OATP1A2 (SLCO1A2) and OCT-1 (SLC22A1) in HepG2 cells following treatment with cholesterol. While CYP3A4 and OATP1A2 expression was unaffected, cholesterol treatment led to increased levels of NTCP and OCT-1 mRNAs. Alterations in the functional characteristics and/or expression levels of drug transporters in the liver may conceivably contribute to the variability in drug oral bioavailability often observed in the clinical settings.

Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus: prevalence and risk factors.

UNLABELLED: Studies show great variation in prevalence of anti-thyroid antibodies in children with type 1 diabetes mellitus (DM1). There still is no consensus regarding screening of autoimmune thyroiditis in patients with DM1, especially in asymptomatic patients. AIM: To investigate the natural history and prevalence of autoimmune thyroiditis in pediatric patients with DM1 and relate it to potential risk factors. PATIENTS AND METHODS: This study is a historical cohort, through research of the records of 474 patients with DM1 from 9 months to 25 years of age, between 1980 and 2005 - 222 boys (46.8%) and 252 girls (53.2%), with an average duration of DM1 of 9.3 +/- 5.8 years. The sample was selected by having at least one measurement of TSH and anti-thyroid autoantibodies (antithyroperoxidase or anti-microssomal and/or anti-thyroglobulin) at any time from diagnosis of DM1. A questionnaire was answered in order to study the variables of interest for the study. Thyroid function disorder was defined as altered levels of TSH, with or without altered free T4 levels. RESULTS: A total of 383 patients (9 months to 25 years of age) were studied, 199 girls (52%) and 184 boys (48%). Sixty-four (16.7%) had positive anti-thyroid antibodies, predominantly girls (p = 0.064). Average duration of DM1 was 9.3 +/- 5.8 years and those above this age had a higher incidence of thyroiditis (p = 0.01). The prevalence of thyroid function disorder in patients with DM1 was 7.3% (n = 28), mostly with thyroiditis (32.8% vs 2.2% with negative antibodies, p < 0.001). There was a positive association between thyroiditis, as well as thyroid function disorders, and other autoimmune disorders (p < 0.001 and p < 0.02, respectively). CONCLUSIONS: Prevalence of thyroiditis in the diabetic population is considerably higher than in the general population. Annual laboratory determinations of anti-TPO antibodies and dosage of TSH should be part of routine tests in the diabetic population, especially in girls, children with DM1 for > 9 years, patients above 12 years of age, and those in whom DM1 is associated with another autoimmune disease. Anti-thyroid antibody positivity may indicate the necessity for thyroid function testing at shorter intervals.

Analysis of the PAX8 gene in 32 children with thyroid dysgenesis and functional characterization of a promoter variant.

BACKGROUND: The molecular basis underlying the development of thyroid dysgenesis remains largely unknown. The objective of this study was to analyze the PAX8 gene in 32 children with congenital hypothyroidism due to thyroid dysgenesis for mutations, and to characterize the functional consequences of the mutations. METHODS: The 5'-untranslated region and the entire coding region of the PAX8 gene were analyzed in 32 children. Functional analyses with a reporter gene assay were performed in transfected PCCL3 and TSA cells. RESULTS: Thirty children did not have any sequence alterations. Two individuals had a previously identified monoallelic cytosine to thymine transition at position -983 in the promoter (-983C>T; mutant P. A of the ATG of the initiator codon is designated as +1), and a novel guanine to cytosine transversion in the non-coding exon 1 (-465G>C; mutant E). Functional analysis revealed that the basal transcriptional activity of the mutants is decreased compared to the wild type. Gel mobility shift assays indicated that mutant P does not interact with a transacting factor whose nature remains to be elucidated. The DNA binding property of mutant E were similar compared to the wild type. CONCLUSIONS: These results suggest that mutations in PAX8 are most likely a very rare cause of thyroid dysgenesis. The observed sequence alterations result in diminished transcriptional activity and, in conjunction with other genetic and non-genetic modifiers, they may contribute to the pathogenesis of thyroid hypoplasia and hypothyroidism.

Classification of Patient Care Complexity: Cloud Technology.

Presentation of the computerized structure to implement, in a university hospital in the South of Brazil, the Patients Classification System of Perroca, which categorizes patients according to the care complexity. This solution also aims to corroborate a recent study at the hospital, which evidenced that the increasing workload presents a direct relation with the institutional quality indicators. The tools used were the Google applications with high productivity interconnecting the topic knowledge on behalf of the nursing professionals and information technology professionals.

[Etiological assessment of hyperthyrotropinemia in children with Down's syndrome]. / Avaliação etiológica da hipertirotropinemia em crianças com síndrome de Down.

OBJECTIVE: To study the prevalence of increased TSH level and its probable cause in children with Down's syndrome treated at Policlínica Antônio Cândido. METHODS: The data were collected using medical records of 169 patients. Of these, 46 patients, whose TSH increased at some time during their follow-up, were re-evaluated. In these patients, TSH, free T4, total T4 and thyroid peroxidase autoantibody (anti-TPO) levels were measured. Thyroid ultrasound, iodine-131 scintigraphy, and a perchlorate discharge test were performed. RESULTS: In 169 children, 86 (50.8%) of whom were male, aged between 1-16 years (median 4 years), 67 (39.6%) presented increased TSH levels. Out of these 67 patients, 46 were prospectively studied. In 31 (67.4%) of them serum TSH returned to normal levels; in 11, TSH remained between 5 and 10 microU/ml, three (6.5%) had a TSH level over 10 microU/ml and one (2.2%) had hyperthyroidism. The diagnoses in 34 patients who were fully studied were: goiter in five (14.7%); Hashimoto's thyroiditis in four (5.9%); hypoplasia in three (8.8%) and iodide organification defect in one (2.9%). The increased TSH levels had a statistically positive relationship with anti-TPO (p = 0.02), but not with gender, abnormal ultrasound or scintigraphy findings. TSH levels did not have any relationship with persistent hyperthyrotropinemia. CONCLUSIONS: In patients with Down's syndrome, slightly elevated and transient TSH levels are frequently detected. Positive anti-TPO antibody test is a key factor in the follow-up of these patients because of its potential risk of progression to manifest thyroid disease.

[Congenital transient hypothyroidism: characteristics of children identified at Newborn Screening Program of the State of Minas Gerais, Brazil]. / Hipotiroidismo congênito transitório: perfil das crianças identificadas no Programa Estadual de Triagem Neonatal de Minas Gerais, Brasil.

Early diagnosis and treatment of congenital hypothyroidism are the main goals of the neonatal screening programs. A retrospective analysis was carried out to assess the characteristics and etiologies of congenital transient hypothyroidism (CTH) in the Newborn Screening Program of the State of Minas Gerais, Brazil. To reach a diagnosis of CTH, altered screening and serum confirmatory T4 and TSH tests and normal serum free T4 and TSH at 4 and 8 weeks after the withdrawal of levothyroxine were used. We studied 21 children with CTH who represented 4.23% of the whole group with detected hypothyroidism and followed them up in the Screening Program. These patients received LT4 therapy for a variable period of one month to three years. Serum confirmatory TSH levels varied from 10.4 to 583.4 microUI/mL. Maternal antibodies, TRAB and anti-TPO, were associated to CTH in two children and iodine overload in one of them. We concluded that CTH is an important component in neonatal screening and hormonal treatment during the first months of the life is essential. The TSH initial levels are not relevant to determine whether the thyroid dysfunction is transient or permanent.

[Utilization of classification in the practice and teaching of nursing. The Brazilian experience]. / Utilização da classificação na prática e no ensino de enfermagem experiência Brasileira.

The authors describe the strategies used for the construction and implementation of a classification model computerized used in the nurses' of an academical hospital daily professional. The classification is structured in the theoretical reference of Benedet and Bub (1999) whose taxonomia has for base the theory of the basic needs of Horta (1979), Carpenito (1997) and NANDA (1999). The model constitute a reality in practice and a progress in the production of the knowledge of the Brazilian nursing.

[Use of computers as a tool for the implementation of the nursing process]. / O uso do computador como ferramenta para implementação do processo de enfermagem.

A group of nurses of the Hospital of Clinics of Porto Alegre-RS, aware that the Process of Nursing is a theoretical model that it provides a logical structure and it bases the nursing actions, developed and it implanted a tool to facilitate the implementation of the stages of the nursing Process. This tool is part of a corporate system of attendance to the patient, it's have as focus the Diagnoses and Interventions of Nursing. The model is based on tables with the following contents, basic human needs, signs and symptoms, to cause, diagnoses and nursing interventions. The professionals' access feels through profiles and passwords. The system presents a positive acting as for the aspect activation in the determination of the diagnosis and prescription of the nursing interventions allowing the nurse to be close to the patient.

Physiological implications of NTBI uptake by T lymphocytes.

In iron overload disorders a significant fraction of the total iron circulates in the plasma as low molecular weight complexes not bound to transferrin, known as non-transferrin-bound iron (NTBI). By catalyzing the formation of free radicals, NTBI accumulation results in oxidative stress and cellular damage, being a major cause of organ toxicity. NTBI is rapidly and preferentially cleared from circulation by the liver and the myocardium, the main disease targets in iron overload conditions. We have recently demonstrated that human peripheral blood T lymphocytes take up NTBI in vitro, with a pattern that resembles that of hepatocytes. Since T lymphocytes constitute a numerically important component of the circulating cell pool, these findings support a putative role for this cell type in the systemic protection against iron toxicity. Here we tested the hypothesis that the circulating peripheral blood T lymphocyte pool constitutes an important storage compartment for NTBI and is thus a modifier of NTBI deposition in target organs. First we show that NTBI uptake by human T lymphocytes increases the expression of the iron-storage protein ferritin and of the iron exporter ferroportin via an IRE-dependent mechanism. NTBI retention by T lymphocytes is shown to be critically controlled by the hepcidin-mediated modulation of ferroportin both in vitro and in vivo. Finally, the protective effect of T lymphocytes was tested by analyzing the patterns of iron accumulation in the T lymphocyte-deficient mouse model Foxn1(nu) before and after reconstitution with T lymphocytes by adoptive transfer. The results confirmed a significant increase of liver and pancreas iron accumulation in T lymphocyte-deficient mice. NTBI accumulation in the liver and spleen was prevented by reconstitution with syngeneic T lymphocytes. Altogether, our results demonstrate that T lymphocytes are important components of a circulating "NTBI storage compartment" and show its physiological relevance as a modifier of tissue iron overload.

The role of oxidative stress in Parkinson's disease.

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra. A number of sources and mechanisms for the generation of reactive oxygen species (ROS) are recognized including the metabolism of dopamine itself, mitochondrial dysfunction, iron, neuroinflammatory cells, calcium, and aging. PD causing gene products including DJ-1, PINK1, parkin, alpha-synuclein and LRRK2 also impact in complex ways mitochondrial function leading to exacerbation of ROS generation and susceptibility to oxidative stress. Additionally, cellular homeostatic processes including the ubiquitin-proteasome system and mitophagy are impacted by oxidative stress. It is apparent that the interplay between these various mechanisms contributes to neurodegeneration in PD as a feed forward scenario where primary insults lead to oxidative stress, which damages key cellular pathogenetic proteins that in turn cause more ROS production. Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD. However, therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression. Recent knowledge gained about the specific mechanisms related to PD gene products that modulate ROS production and the response of neurons to stress may provide targeted new approaches towards neuroprotection.