Increased susceptibility of cystic fibrosis airway epithelial cells to ferroptosis

BACKGROUND: Defective chloride transport in airway epithelial cells (AECs) and the associated lung disease are the main causes of morbidity and early mortality in cystic fibrosis (CF). Abnormal airway iron homeostasis and the presence of lipid peroxidation products, indicative of oxidative stress, are features of CF lung disease. RESULTS: Here, we report that CF AECs (IB3-1) are susceptible to ferroptosis, a type of cell death associated with iron accumulation and lipid peroxidation. Compared to isogenic CFTR corrected cells (C38), the IB3-1 cells showed increased susceptibility to cell death upon exposure to iron in the form of ferric ammonium citrate (FAC) and the ferroptosis inducer, erastin. This phenotype was accompanied by accumulation of intracellular ferrous iron and lipid peroxides and the extracellular release of malondialdehyde, all indicative of redox stress, and increased levels of lactate dehydrogenase in the culture supernatant, indicating enhanced cell injury. The ferric iron chelator defer-oxamine (DFO) and the lipophilic antioxidant ferrostatin-1 inhibited FAC and erastin induced ferroptosis in IB3-1 cells. Glutathione peroxidase 4 (GPX4) expression was decreased in IB3-1 cells treated with FAC and erastin, but was unchanged in C38 AECs. Necroptosis appeared to be involved in the enhanced susceptibility of IB3-1 AECs to ferroptosis, as evidenced by partial cell death rescue with necroptosis inhibitors and enhanced mixed lineage kinase domain-like (MLKL) localisation to the plasma membrane. CONCLUSION: These studies suggest that the increased susceptibility of CF AECs to ferroptosis is linked to abnormal intracellular ferrous iron accumulation and reduced antioxidant defences. In addition, the process of ferroptotic cell death in CF AECs does not appear to be a single entity and for the first time we describe necroptosis as a potential contributory factor. Iron chelation and antioxidant treatments may be promising therapeutic interventions in cystic fibrosis.

A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy / 中华医学杂志(英文版)

BACKGROUND@#Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS).@*METHODS@#A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score.@*RESULTS@#A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram.@*CONCLUSIONS@#PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.

Associations between physical activity, sedentary behavior, and health risk behaviors among adolescents from a city in Southern Brazil / Associações entre atividade física, comportamento sedentário e comportamentos de risco à saúde entre adolescentes de uma cidade do Sul do Brasil

This study examined the independent and combined associations of physical activity (PA) and sedentary behavior (SB) with health risk behaviors in Brazilian adolescents. Participants were 893 adolescents (454 girls) from Curitiba, Brazil. The Youth Activity Profile questionnaire evaluated PA and the Adolescent Sedentary Questionnaire evaluated SB. The Youth Risk Behavior Surveillance System ( YRBS) questionnaire evaluated fruit, vegetable, alcohol, and tobacco consumption. Binary Logistic regression measured the independent and combined associations of PA and SB with risk behaviors. PA was inversely associated with low fruit (OR = 0.30; 95%CI: 0.18-0.51) and vegetable consumption (OR = 0.43; 95%CI: 0.25-0.73), and tobacco use (OR = 0.52; 95%CI: 0.29-0.89). However, PA was positively associated with mild (OR = 1.54; 95%CI: 1.08-2.19) and excessive alcohol use (OR = 1.53; 95%CI: 1.01-2.33). Higher levels of PA were associated with reduced risks of smoking and healthier eating patterns, but higher likelihood of alcohol consumption

Este estudo examinou as associações independentes e combinadas de atividade física (AF) e do comportamento sedentário (CS) com comportamentos de risco à saúde em adolescentes brasileiros. Participaram do estudo 893 adolescentes (454 meninas) de Curitiba, Brasil. O questionário Youth Activity Profile avaliou a AF e o Questionário de atividades sedentárias dos adolescentes avaliou o CS. O questionário Youth Risk Behavior Surveillance System (YRBS) avaliou o consumo de frutas, vegetais, álcool e tabaco. A regressão logística binária avaliou as associações independentes e combinadas de AF e CS com comportamentos de risco. AF foi inversamente associado com baixo consumo de frutas (OR = 0,30; IC95%: 0,18-0,51), de vegetais (OR = 0,43; IC95%: 0,25-0,73) e uso de tabaco (OR = 0,52; IC95%: 0,29-0,89). No entanto, a AF foi positivamente associada com uso moderado (OR = 1,54; IC95%: 1,08-2,19) e uso excessivo de álcool (OR = 1,53; IC95%: 1,01-2,33). Níveis mais altos de AF foram associados com riscos reduzidos de fumar e padrões alimentares mais saudáveis e com maior probabilidade de consumo de álcool

Analyzing the Role of the Chemical Hygiene Officer in Scientific Laboratories: A Professional Position on Regulations, Function, and Needs for Program Effectiveness

Work-related hazards and risks continue to be a challenge in workplaces across industry. It is no secret thatengineering and administrative control measures are critical for protecting employees, and despite thisknowledge, protecting employees using properly implemented occupational safety and health (OSH)programs remains to be a continuous challenge. Although fatality rates have decreased over the past severaldecades, the overall numbers of occupational accidents and work-related diseases occurring globallycontinues to be a serious problem. Globally, there are hundreds of millions of occupational injuries anddiseases, both fatal and non-fatal, every year, even in the United States, which has a prevalent and activeagency, the Occupational Safety and Health Administration (OSHA) that addresses OSH. Nevertheless,injury and illness occurs in a great multitude of professions, job tasks, and industries, including in scientificresearch and academic laboratories, which are often left out of the conversation about high-risk industrialenvironments, despite the traditional uses of highly hazardous chemicals and processes. Although twentyyears have elapsed since OSHA refined the scope of the 29 Code of Federal Regulations (CFR) 1910.1200 –Hazard Communication, and promulgated a second right-to-know (RTK) standard, CFR 1910.1450 –Exposure to Hazardous Chemicals in Laboratories to specifically address requirements for limiting chemicalexposure at laboratory scale, the required designation within the OSHA Lab Standard of a chemical hygieneofficer (CHO) is singularly insufficient to implement an effective chemical hygiene plan (CHP).

GoldCLIP: Gel-omitted Ligation-dependent CLIP / 基因组蛋白质组与生物信息学报·英文版

Protein-RNA interaction networks are essential to understand gene regulation control. Identifying binding sites of RNA-binding proteins (RBPs) by the UV-crosslinking and immunoprecipitation (CLIP) represents one of the most powerful methods to map protein-RNA interactions in vivo. However, the traditional CLIP protocol is technically challenging, which requires radioactive labeling and suffers from material loss during PAGE-membrane transfer procedures. Here we introduce a super-efficient CLIP method (GoldCLIP) that omits all gel purification steps. This nonisotopic method allows us to perform highly reproducible CLIP experiments with polypyrimidine tract-binding protein (PTB), a classical RBP in human cell lines. In principle, our method guarantees sequencing library constructions, providing the protein of interest can be successfully crosslinked to RNAs in living cells. GoldCLIP is readily applicable to diverse proteins to uncover their endogenous RNA targets.

Utilization of the oncoscan microarray assay in cancer diagnostics

Current strategies for cancer patient management include the use of genomic and proteomic test results to help guide therapeutic selection. The need for multi-target variant analysis is highlighted by the growing number of novel therapies to treat tumors with specific profiles and the increasing recognition that cancer is an extremely heterogeneous syndrome. Microarray analysis is a powerful genomic tool that provides genome-wide genetic information that is critical for guiding cancer treatments. Unlike constitutional applications of microarray analysis which are performed on whole blood samples, microarray analysis of solid tumors is challenging because tumor tissues are typically formalin fixed and paraffin embedded (FFPE). Genomic DNA extracted from FFPE tissues can also be fragmented into small pieces and yield much lower concentrations of DNA. We validated and implemented the Affymetrix OncoScan® FFPE assay to enable genome-wide analysis from these types of samples. The Affymetrix OncoScan® assay utilizes molecular inversion probes that generate multiplexed array hybridization targets from as short as 40 base-pairs of sequence and as low as approximately 80 ng of genomic DNA. OncoScan microarray analysis provides genomic information that includes structural variations, copy number variations and SNPs in a timely and a cost-effective manner from FFPE tumor tissues (AU)

Development of an Ex Vivo Model for the Study of Cerebrovascular Function Utilizing Isolated Mouse Olfactory Artery

OBJECTIVE: Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. METHODS: The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately -500 microm in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). RESULTS: We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin PGH2. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. CONCLUSION: Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.

Response-Inhibition Capacity and Short-Term Memory are Robust to the Effects of High Fat Diet (HFD) during Pre and Periadolescence / La capacidad de inhibición de respuesta y la memoria a corto plazo son robustos a los efectos de la dieta alta en grasa (HFD) durante la pre y periadolescencia

Se tiene evidencia que la exposición a una dieta alta en grasa puede ser perjudicial para la cognición a lo largo de la vida. Hemos demostrado previamente que el aprendizaje contexto-estímulo es sensible a los efectos de una dieta alta en grasas durante la adolescencia, pero no la edad adulta. En el presente estudio se determinó si la exposición a una dieta alta en grasa en la pre y peri adolescencia interfiere con la capacidad de respuesta de inhibición, el aprendizaje de reglas, y la memoria en la edad adulta. Las ratas fueron alimentadas con una grasa alta o dieta baja en grasa durante la pre y periadolescencia y se completaron las pruebas de comportamiento como adultos para evaluar la capacidad de respuesta de inhibición y eficacia reforzador regla-aprendizaje y la memoria a corto plazo. Los resultados indican que la dieta rica en grasas durante la pre y periadolescencia puede tener efectos a largo plazo sobre la eficacia del refuerzo y la atención sostenida. Sin embargo, los resultados indican que o bien el periodo de pre y periadolescencia es demasiado corto para que una dieta alta en grasas pueda inducir déficits a largo plazo en la respuesta de inhibición, regla de aprendizaje o la memoria, o que la maduración en ausencia de una dieta alta en grasas rescate a los individuos de estos déficits.

Several lines of evidence demonstrate that high fat diet exposure can be detrimental to cognition across the lifespan. We have previously shown that context-stimulus learning is sensitive to high fat diet effects during adolescence but not adulthood. In the present study we determined if pre and periadolescent high fat diet exposure interferes with response -inhibition capacity, rule - learning, and memory during adulthood. Rats were fed a high fat or low fat diet during pre and periadolescence and completed behavioral testing as adults to assess response -inhibition capacity and reinforcer efficacy rule-learning and short-term memory. Results indicate pre and periadolescent high fat diet may have long-term effects on reinforcer efficacy and sustained attention. However, results indicate that either the pre and periadolescence period is too short for a high fat diet to induce long-term deficits in response-inhibition, rule -learning, or memory, or that maturation in the absence of a high fat diet rescued these deficits.

Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

Review of current indications for combined very high fluence collagen cross-linking and laser in situ keratomileusis surgery.

In this brief review we will discuss the reasoning and evolution of our current use of combined very high-fluence collagen crosslinking and laser in situ keratomileusis. Several presentations and pertinent publications are reviewed, along with the key steps of the enhanced LASIK procedure. Long term outcome data support the safety and efficacy of LASIK Xtra in stabilizing myopic but also hyperopic LASIK results. In conclusion, we have compelling evidence that LASIK Xtra is a safe and effective adjunct.

Biomechanical Comparison of an Intramedullary and Extramedullary Free-Tissue Graft Reconstruction of the Acromioclavicular Joint Complex

BACKGROUND: Several different surgical techniques have been described to address the coracoclavicular (CC) ligaments in acromioclavicular (AC) joint injuries. However, very few techniques focus on reconstructing the AC ligaments, despite its importance in providing stability. The purpose of our study was to compare the biomechanical properties of two free-tissue graft techniques that reconstruct both the AC and CC ligaments in cadaveric shoulders, one with an extramedullary AC reconstruction and the other with an intramedullary AC reconstruction. We hypothesized intramedullary AC reconstruction will provide greater anteroposterior translational stability and improved load to failure characteristics than an extramedullary technique. METHODS: Six matched cadaveric shoulders underwent translational testing at 10 N and 15 N in the anteroposterior and superoinferior directions, under AC joint compression loads of 10 N, 20 N, and 30 N. After the AC and CC ligaments were transected, one of the specimens was randomly assigned the intramedullary free-tissue graft reconstruction while its matched pair received the extramedullary graft reconstruction. Both reconstructed specimens then underwent repeat translational testing, followed by load to failure testing, via superior clavicle distraction, at a rate of 50 mm/min. RESULTS: Intramedullary reconstruction provided significantly greater translational stability in the anteroposterior direction than the extramedullary technique for four of six loading conditions (p < 0.05). There were no significant differences in translational stability in the superoinferior direction for any loading condition. The intramedullary reconstructed specimens demonstrated improved load to failure characteristics with the intramedullary reconstruction having a lower deformation at yield and a higher ultimate load than the extramedullary reconstruction (p < 0.05). CONCLUSIONS: Intramedullary reconstruction of the AC joint provides greater stability in the anteroposterior direction and improved load to failure characteristics than an extramedullary technique. Reconstruction of the injured AC joint with an intramedullary free tissue graft may provide greater strength and stability than other currently used techniques, allowing patients to have improved clinical outcomes.

The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma

PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A or C-->T) rather than a transversion mutation (G-->T or G-->C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.

Aplicação do modelo de Rasch na medida de transtornos da personalidade / Application of the Rasch model in measuring personality disorders

OBJECTIVE: To describe item and person parameters obtained with the Rasch model, one of the item response theory models, in the assessment of personality disorders based on Millon's theory. METHOD: A total of 350 people participated in the study. Age ranged from 18 to 67 years (mean ± standard deviation = 27.02±10.13), and 71.7% of the participants (n = 251) were female. Of the 350 individuals, 21.1% (n = 74) answered affirmatively about being under psychiatric treatment and taking psychiatric medications. The Personality Disorders Dimensional Inventory (PDDI), an instrument designed to assess personality disorders according to Millon's theory, was applied to all participants. Data were analyzed using the Rasch model. RESULTS: Overall, analysis with the Rasch model revealed that the PDDI has adequate psychometric properties for the assessment of personality disorders. CONCLUSION: Among the contributions of item response theory models for clinical instruments, the Rasch person-item map deserves to be highlighted as a successful attempt to improve the understanding of clinical scores obtained in response to particular test items.

OBJETIVO: Descrever os parâmetros de itens e pessoas obtidos com o modelo de Rasch, um dos modelos da teoria de resposta ao item, na avaliação de transtornos da personalidade de acordo com a teoria de Millon. MÉTODO: Participaram do estudo 350 pessoas. A idade variou de 18 a 67 anos (média ± desvio padrão = 27.02±10.13), e 71.7% (n = 251) eram do sexo feminino. Dos 350 participantes, 21.1% (n = 74) responderam afirmativamente sobre estarem em tratamento psiquiátrico e utilizarem medicamento psiquiátrico. O Inventário Dimensional de Transtornos da Personalidade (IDTP), destinado à avaliação dos transtornos da personalidade com base na teoria de Millon, foi aplicado a todos os participantes. Os dados foram analisados por meio do modelo de Rasch. RESULTADOS: De modo geral, os resultados da análise por meio do modelo de Rasch revelaram que o IDTP tem parâmetros psicométricos adequados para a avaliação de transtornos da personalidade. CONCLUSÃO: Entre as contribuições da teoria de resposta ao item para instrumentos clínicos, o mapa de pessoas-itens do modelo Rasch merece destaque enquanto tentativa bem-sucedida de aumentar a compreensão das pontuações clínicas obtidas em resposta a determinadas questões de um teste.

HIV and hepatitis C co-infection

Improved antiretroviral therapy (ART) has reduced HIV-related morbidity and improved survival. Such improvements have led to an increasing contribution of non-HIV related disease to overall morbidity among people with HIV. HIV/HCV co-infection and its associated liver disease is an emerging clinical management issue, particularly in settings of high co-infection prevalence. Treatment for HCV infection in HIV infected individuals is with pegylated interferon and ribavirin therapy. Sustained virological response to therapy is achieved in around 40%, which is 10-20% lower than in HCV monoinfection and therapy may be complicated by issues of drug interactions and significant toxicity. However, greater understanding of baseline factors can contribute to better prediction of treatment outcome, and monitoring of on-treatment virological responses increasingly allows individualisation of therapy. Where possible, treatment of HCV is often advisable before HAART is required to avoid the issues of drug interactions on HCV therapy and the risk of HAART related hepatotoxicity. Early diagnosis of both HIV and HCV-infection is essential to most effectively manage HIV-HCV co-infected individuals. New therapies, including HCV protease and polymerase inhibitors, are in development and may widen therapeutic options for HIV/HCV co-infected individuals in the future.

Vaccines against periodontitis: a forward-looking review

Periodontal disease, as a polymicrobial disease, is globally endemic as well as being a global epidemic. It is the leading cause for tooth loss in the adult population and has been positively related to life-threatening systemic diseases such as atherosclerosis and diabetes. As a result, it is clear that more sophisticated therapeutic modalities need to be developed, which may include vaccines. Up to now, however, no periodontal vaccine trial has been successful in satisfying all the requirements; to prevent the colonization of a multiple pathogenic biofilm in the subgingival area, to elicit a high level of effector molecules such as immunoglobulin sufficient to opsonize and phagocytose the invading organisms, to suppress the induced alveolar bone loss, or to stimulate helper T-cell polarization that exerts cytokine functions optimal for protection against bacteria and tissue destruction. This article reviews all the vaccine trials so as to construct a more sophisticated strategy which may be relevant in the future. As an innovative strategy to circumvent these barriers, vaccine trials to stimulate antigen-specific T-cells polarized toward helper T-cells with a regulatory phenotype (Tregs, CD4+, CD25+, FoxP3+) have also been introduced. Targeting not only a single pathogen, but polymicrobial organisms, and targeting not only periodontal disease, but also periodontal disease-triggered systemic disease could be a feasible goal.

Iron deficiency decreases hemolysis in sickle cell anemia / Anemia ferropriva diminui hemólise em anemia falciforme

A woman with homozygous sickle cell disease developed severe iron deficiency due to long-standing uterine bleeding. At this point, the serum lactic dehydrogenase level was normal and the reticulocyte count was only minimally elevated. This suggested that the low red cell hemoglobin concentration that resulted from iron deficiency also decreased Hb S polymerization and lowered the hemolytic rate. Iron replacement led first to a substantially improved hemoglobin concentration with only a minimal increase in the hemolytic rate and secondarily to a modest further improvement in the hemoglobin concentration and a marked increase in the hemolytic rate. The hematologic changes observed in this patient, and those in other iron deficient sickle cell patients reported in the literature, suggest that it may be appropriate to consider the induction of an intermediate iron deficient stage as experimental treatment in adult sickle cell patients.

Uma mulher com anemia falciforme homozigose para a Hb S evoluiu com anemia ferropriva grave devido a sangramento uterino prolongado. A dosagem de dehidrogenase lática era normal e a contagem de reticulócitos estava levemente aumentada. Isto sugere que concentrações baixas de hemoglobina, que resulta de anemia ferropriva, também diminuem a polimeração de Hb S e reduz a taxa de hemólise. O complemento de ferro levou, primeiramente, a uma concentração substancialmente maior de hemoglobina com apenas um aumento mínimo na taxa hemolítica e subsequentemente a um aumento leve adicional na concentração da hemoglobina e um aumento notável na taxa hemolítica. As mudanças hematológicas observadas nesta paciente e aquelas em outras pacientes com anemia falciforme e também deficientes de ferro relatadas na literatura sugerem que pode ser interessante considerar a indução de deficiência de ferro como tratamento experimental em pacientes adultos com anemia falciforme.

Evaluation of oxidative stress in experimental rabbit aneurysms / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the roles of oxidative stress in the generation and development of aneurysms.</p><p><b>METHODS</b>Five terminal aneurysms and 8 lateral aneurysms were rebuilt on rabbits, and 6 normal artery vessels were prepared as control. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and anti-reactive oxygen species unit (anti-ROS unit) were measured with chemical methods.</p><p><b>RESULTS</b>The levels of MDA in terminal and lateral aneurysms were (33.85 +/- 8.66) and (27.87 +/- 5.78) nmol/mg prot, respectively, which were significantly higher than (10.91 +/- 2.72) nmol/mg prot in control group (P < 0.01). The levels of SOD in terminal and lateral aneurysms were (28.30 +/- 3.58) and (33.00 +/- 8.09) U/mg prot, respectively, which were significantly lower than (127.27 +/- 38.72) U/mg prot in control group (P < 0.01). The levels of anti-ROS unit in terminal and lateral aneurysms were (47.86 +/- 5.00) and (62.64 +/- 13.87) U/ mg prot, respectively, which were significantly lower than (116.94 +/- 9.22) U/mg prot in control group (P < 0.01). No significant differences were shown between terminal aneurysm and lateral aneurysm in MDA and SOD except anti-ROS unit (P = 0.014). MDA had negative correlations with both SOD and anti-ROS unit, and the correlation coefficients were -0. 830 and -0. 852, respectively.</p><p><b>CONCLUSION</b>Oxidative stress may play an important role in the development of aneurysms. Oxidative stress seems similar among various aneurysms.</p>