bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nephrotoxic effects of di-(2-ethylhexyl)phthalate (DEHP) hydrolysis products on cultured kidney epithelial cells
Authors: Rothenbacher Klaus-Peter , Kimmel Reiner , Hildenbrand Sibylle , Schmahl Friedrich W , Dartsch Peter C 
Published: January 2017

1 Di-(2-ethylhexyl)-phthalate (DEHP) possesses a great industrial value as a plasticizing agent and has become an ubiquitous environmental contaminant. In most species it is rapidly metabolized to mono-(2-ethylhexyl)-phthalate (MEHP) and 2-ethylhexanoic acid (2- EHA). Evaluation of toxicity of DEHP and its primary metabolites has been focussed on reproductive toxicity and hepatocarcinogenic properties. The aim of this study was to determine the nephrotoxic potential of both DEHP metabolites by use of cultured kidney epithelial cells (Opossum kidney cells; OK cells). 2 For this purpose, OK cells were exposed for 3 days to MEHP and 2-EHA at concentrations ranging from 0.1 -500 mmol/L and the toxicity as well as the effects on migratory activity and intracellular cytoskeleton were studied by cell biological, morphological and morpho-metric methods. 3 When compared with corresponding controls, treatment of OK cells with MEHP and 2-EHA, respectively, showed marked differences in cell viability between both DEHP metabolites. MEHP caused a dose-depen-dent decrease in cell viability (ED50 =25 mmol/L) accompanied by a moderate swelling of the cells at concentrations up to 25 mmol/L. MEHP concentrations higher than 25 mmol/L caused a dose-dependent shrinkage of the cells and the occurrence of a high amount of cell debris as a result of cell lysis. 2-EHA did not cause a reduced viability or an altered cell volume. The migratory activity of OK cells was not significantly influenced by both metabolites. Moreover, MEHP toxicity resulted in a largely reduced and altered organization of F-actin (stress fibers), but not of myosin, microtubules and vimentin. 4 The study indicates that cultured epithelial cells can be used as a prescreening system to assess the nephrotoxicity of hazardous substances such as DEHP. As demonstrated in this study, only MEHP, but not 2-EHA, has a marked nephrotoxic effect in vitro.
Prognostic implications of hyperkalemia in toad toxin intoxication
Authors: Chi Huan-Teng , Hung Dong-Zong , Hu Wei-Hsiung , Yang Dar-Yu 
Published: January 2017

The toad possesses several toxic substances. Toad toxin poisoning manifests itself primarily with digitalis-like, cardioactive effects which results in bradycardia, varying degrees of atrio-ventricular block, ventricular tachycardia, ventricular fibrillation and sudden death. We report a cluster poisoning in a family who became intoxicated after ingestion of cooked toad soup for a skin problem. The youngest one (15 months old) died of refractory bradydyarrhythmias soon after arriving at our hospital. A second child (20 months old), who survived, arrived in shock with hyperkalemia (potassium 7.3 mEq/ L) and varying degrees of atrio-ventricular block. She was successfully treated with atropine, lidocaine, and cardio-version, and had a transvenous temporary pacemaker implanted for 1 day. The third boy (16 years old) had hyperkalemia (potassium 6.3 mEq/L) and bradycardia. The remaining three adults had only mild symptoms of nausea, vomiting, watery diarrhea and a sensation of numbness over their oral mucosa. We found that the level of serum potassium had prognostic implications in toad intoxication. Determination of serum potassium level is readily available in almost every hospital and is therefore more convenient to measure than serum digoxin level. We conclude that if hyperkalemia develops, the treatment of toad intoxication must be more aggressive to prevent mortality.
The pharmacokinetics and metabolism of 14C/13C-labeled ortho-phenylphenol formation following dermal application to human volunteers
Authors: Timchalk C , Selim S , Sangha G , Bartels M J 
Published: January 2017

1. The pharmacokinetics and metabolism of uniformly labeled 14C/13C-ortho-phenylphenol (OPP) were followed in six human male volunteers given a single 8 h dermal dose of 6 mg OPP/kg body weight formulated as a 0.4% (w/v) solution in isopropyl alcohol. The application site was covered with a non-occlusive dome allowing free movement of air, but preventing the loss of radioactivity due to physical contact. At 8 h post-exposure the non-occlusive dome was removed, the dose site was wiped with isopropyl alcohol containing swabs and the skin surface repeatedly stripped with tape. Blood specimens, urine, and feces were collected from each volunteer over a 5 day post-exposure period and were analyzed for radioactivity and metabolites (urine only). 2. Following dermal application, peak plasma levels of radioactivity were obtained within 4 h post-exposure and rapidly declined with virtually all of the absorbed dose rapidly excreted into the urine within 24 h post-exposure. A one-compartment pharmacokinetic model was used to describe the time-course of OPP absorption and clearance in male human volunteers. Approximately 43% of the dermally applied dose was absorbed through the skin with an average absorption half-life of 10 h. Once absorbed the renal clearance of OPP was rapid with an average half-life of 0.8 h. The rate limiting step for renal clearance was the relatively slower rate of dermal absorption; therefore the pharmacokinetics of OPP in humans was described by a `flip-flop' single compartment model. Overall, the pharmacokinetics were similar between individuals, and the model parameters were in excellent agreement with the experimental data. 3. Approximately 73% of the total urinary radioactivity was accounted for as free OPP, OPP-sulfate and OPP-glucuronide conjugates. The sulfate conjugate was the major metabolite (*69%). Therefore, total urinary OPP equivalents (acid-labile conjugates+free OPP) can be used to estimate the systemically absorbed dose of OPP. 4. The rapid excretion of OPP and metabolites into the urine following dermal exposure indicates that OPP is unlikely to accumulate in humans upon repeated exposure. Based on these data, blood and/or urinary OPP concentration (acid-labile conjugates) could be utilized to quantify the amount of OPP absorbed by humans under actual use conditions.
Medicinal herb, Thonningia sanguinea protects against aflatoxin B1 acute hepatotoxicity in Fischer 344 rats
Authors: Gyamfi Maxwell Afari , Aniya Yoko 
Published: January 2017

1. Thonningia sanguinea, a plant used prophylactically against bronchial asthma in Ghana was recently found to have antioxidative and hepatoprotective actions in our laboratory. 2. In this study, the effect of T. sanguinea extract on certain biochemical indices in serum and liver of Fischer 344 rats given a single intraperitoneal (i.p.) dose (1 mg/kg) of aflatoxin B1 (AFB1) was investigated. 3. Administration of AFB1 resulted in significant increases in serum alanine aminotransferase (ALT) and glutathione S-transferase (GST) levels and a signifi-cant decrease in aniline hydroxylase activity in liver microsomes. When T. sanguinea (5 ml/kg) was intraperitoneally administered to rats 12 h and 1 h before AFB1, liver injury was significantly reduced as seen in the decreased levels of serum ALT and serum GST. However, the decrease in aniline hydroxylase activity by AFB1 was not recovered but enhanced by T. sanguinea pre-treatment. 4. Kinetic analysis of cytochrome P450 activity of rat liver microsomes in vitro demonstrated that T. sanguinea inhibited aniline hydroxylase non-competitively suggesting depression of biotransformation of AFB1 to toxic metabolites. 5. The data indicate a hepatoprotective action of T. sanguinea against AFB1-induced liver injury.
Molecular analyses of adaptive survival responses (ASRs): role of ASRs in radiotherapy
Authors: Boothman David A , Odegaard Eric , Yang Chin-Rang , Hosley Kelly , Mendonca Marc S 
Published: January 2017

Adaptive survival responses (ASRs), whereby cells demonstrate a survival advantage when exposed to very low doses of ionizing radiation (IR) 4-24 h prior to a high dose challenge, were first reported over 15 years ago. These responses were linked to hormesis, which implied that exposure to low levels of IR may be beneficial to the cell. We postulate that increased survival does not necessarily mean that the treatment is beneficial. Studies at the molecular level indicate that ASRs are the result of misregulated cell cycle checkpoint responses, occurring in the G1 phase of the cell cycle after IR. Specific gene products (i.e., PCNA, cyclin D1, cyclin A, XIP8, xip5 and xip13) appear to control these cell cycle checkpoint responses. Certain neoplastic cells show potent ASRs because they bypass checkpoints which would otherwise lead to apoptosis or other forms of cell death (possibly necrosis), and/or these cancer cells lack genetic factors, such as specific caspases (cysteine aspartate-specific proteases), that control apoptosis. Alterations in these cell cycle checkpoints or apoptotic responses may also occur during IR-induced stress responses in normal cells, at critical times (10-18 days posttreatment) following IR. One IR-induced protein, XIP8, may be a critical controlling factor at this point where delayed-onset apoptosis occurs. Additionally, we have shown that the presence or absence (i.e., SCID cells) of nonhomologous DNA double strand break repair did not seem to influence ASRs, suggesting that ASRs may be caused by signal transduction stress responses. ASRs may be beneficial to survival, however, the consequence(s) of that survival may be dire. For example, many neoplastic cells exhibited far greater ASRs than normal cells. Additionally, ASRs were induced by as little as 1 cGy and and were enhanced by repeated exposures of low level radiation. The implications for radiotherapy are that when a patient arrives for port film imaging during the course of therapy, the dose-rate, overall level of exposure, and time between port film exposure and high dose IR treatment become potentially important factors for improved efficacy of treatment of certain cancers. Further research is warranted to determine what molecular factors are most important for ASRs, and current work is focusing on XIP8.
Hormesis - Implications for risk assessment caloric intake (body weight) as an exemplar
Authors: Turturro Angelo , Hass Bruce , Hart Ronald W 
Published: January 2017

Hormesis can be considered as a parameter which has a non-monotonic relationship with some endpoint. Since caloric intake is such a parameter, and the impact of this parameter on risk assessment has been fairly well characterized, it can provide clues as to how to integrate the information from a hormetic parameter into risk assessments for toxicants. Based on the work with caloric intake, one could: (a) define a biomarker for hormetic effect; (b) integrate specific information on when in the animals lifespan the parameter is active to influence parameters such as survival; (c) evaluate component effects of the overall hormetic response; and (d) address the consequences of a non-monotonic relationship between the hormetic parameter and endpoints critical for risk assessment. These impacts on risk assessments have been characterized for chronic tests, but are also true for short-term tests. A priority is the characterization of the dose-response curves for hormetic parameters. This quantification will be critical in utilizing them in risk assessment. With this information, one could better quantitatively address the changes one expects to result from the hormetic parameter, and limit the uncertainty and variability which occurs in toxicity testing.
Measurement of the Costs in Two Mammographic Screening Programmes in the Province of Florence, Italy
Authors: Zappa Marco , Spagnolo Gianfranco , Ciatto Stefano , Giorgi Daniela , Paci Eugenio , Del Turco Marco Rosselli 
Published: January 2017

Objectives – To estimate and to compare the cost per woman examined and per breast cancer detected in two mammographic screening programmes in the province of Florence. Setting –Two ongoing, population based, mammographic screening programmes in the province of Florence. The first (district project) was started in the seventies in a rural area, whereas the second (city project) was started in the city at the end of 1990. Methods –All relevant resources consumed by the programmes (costs) were listed and measured. The costs are related to 1993. The unit cost for each phase (recruitment, screening, assessment) of the screening process was estimated by dividing the total cost of the phase by the number of women examined. The cost per cancer detected was obtained by dividing the total cost of the programme by the number of cancers detected at screening. Results –The costs per woman examined were $38.1 and $41.1 in the district and city programmes respectively. The cost per breast cancer detected was $7424 in the district programme and $5180 in the city programme. Staff acccounted for more than 50% of the total cost. The unit cost in the screening phase was higher in the district programme, whereas it was lower in the assessment phase. Conclusions –Our results are consistent with, although slightly lower than, published estimates of the cost per woman screened. Important parameters for determining the efficiency of a mammographic screening programme are the compliance rate and the recall rate.
Compliance after 17 Years of Breast Cancer Screening
Authors: Scaf-Klomp W , van Sonderen F L P , Stewart R , van Dijck J A A M , van den Heuvel W J A 
Published: January 2017

Objective –To investigate changes in attendance over the course of a population based breast screening programme. Design – Longitudinal; analysis of registered data over nine screening rounds. Setting –Subjects belong to the screening population of the Nijmegen experimental breast screening programme (1975–1990). Subjects –A cohort of 6898 women who were enrolled in 1975 at the age of 50–69 years and who were invited to nine subsequent screening rounds, irrespective of their attendance at previous rounds. Results –Attendance of women aged 50–53 years at entry was high at the initial screening (88%), decreased in the course of the programme, but remained well over 60% until round 8; 39% completed nine rounds and 24% completed seven to eight rounds. Attendance of women who were older at entry was somewhat lower at the initial screening (87%–82%) and declined more strongly. Regular compliance was also lower. Specific compliance patterns are found that can be relevant for further research. Conclusions –A substantial proportion of eligible women can be committed to mammography every two years, possibly even after reaching the age of 70, if the age at entry is around 50 and the screening programme is well established in the community. Starting a screening programme in older women seems ineffective.
Screening for Down's Syndrome: The First Two Years Experience in Bristol
Authors: Goldie D J , Astley J P , Beaman J M , Bickley D A , Gunneberg A , Jones S R 
Published: January 2017

Objectives – To evaluate the effectiveness of a programme for antenatal screening for Down's syndrome using a fetoprotein and total human chorionic gonadotrophin as maternal serum markers. Setting –A district general hospital providing a screening service to a local purchasing authority and (under contract) to another purchasing authority in the same region. Methods – Patients were counselled and screened between 15 and 20 weeks gestation and Down's risk estimates calculated using the maternal serum marker results as modifiers of the age related risk. Outcome was determined in collaboration with the Regional Cytogenetics Unit. Outcome Measures – Detection rate for Down's syndrome, false positive rate, uptake of screening, and uptake of amniocentesis. Results– In two years 22 816 women were screened (approximately 84% of population); 32 Down's pregnancies were identified, 19 (59.4%) had a reported risk of ≥1:250 and 20 (62.5%) a reported risk of ≥1:300. Of those screened before 17 weeks, 16/20 (80%) had a reported risk of ≥1: 300 compared with 4/12 (33%) of those screened later (P = 0.008); 4.64% of patients screened had reported risks ≥1: 250 and 5.87% reported risks of ≥ 1:300. Amniocentesis uptake was 70% in patients with reported risks of ≥ 1:300. Conclusions –Overall the screening programme was effective but screening before 17 weeks was very much more effective than screening later.
Metachronous Occurrence of Colorectal Cancer in a Muir-Torre Syndrome Patient Presenting with Recurrent Sebaceous Adenoma of the Eyelid: Case Report and Updated Review of the Literature
Authors: Agiannidis Christos , Pana Zoe D. , Molyva Dimitra , Kalokasidis Konstantinos , Mixiou Maria 
Published: January 2017

Background: Muir-Torre syndrome (MTS) is a rare genodermatosis considered a subtype of hereditary nonpolyposis colorectal cancer and traditionally associated with mutations in the mismatch repair genes. Objective: We describe a 51-year-old male with primary manifestations of recurrent sebaceous adenoma of the upper eyelid, a positive cancer family history, and metachronous occurrence of colorectal cancer. Method: The diagnosis of MTS was established based on the clinical course, family history, and histopathologic findings, although further immunohistologic testing revealed the absence of MSH2 mutation. We additionally performed an updated summary of published MTS cases with sebaceous neoplasms originating from the eyelid and conjunctiva for the period 2005 to 2011. Conclusion: This patient, the second Greek case described in the international literature, is of interest mainly because of the metachronous occurrence of the visceral malignancy in combination with the absence of MSH2 mutation. The need for high clinical suspicion for MTS in cases with sebaceous lesions of the periocular region should therefore be reinforced regardless of the mutational screening test undertaken. Contexte: Le syndrome de Muir-Torre (SMT) est une génodermatose rare, considérée comme un sous-type du cancer colorectal héréditaire, non polyposique, et habituellement associée à des mutations des gènes de réparation des mésappariements. Objectif: Nous faisons état ici du cas d'un homme de 51 ans, présentant l'accumulation de faits suivants: manifestations primaires d'adénome sébacé récidivant de la paupière supérieure, antécédents familiaux de cancer, et apparition asynchrone d'un cancer colorectal. Méthode: Le diagnostic de SMT a été posé à partir de l'évolution clinique, des antécédents familiaux, et de l'examen histopathologique, bien que les analyses immunohistologiques ultérieures aient révélé l'absence de mutation du gène MSH2. Nous avons également procédé à la mise à jour d'un résumé de cas publiés de SMT, accompagné de néoplasmes sébacés prenant naissance dans la paupière et la conjonctive, qui se sont produits durant la période de 2005 à 2011. Conclusion: Ce qui fait surtout l'intérêt du présent cas, le deuxième cas grec décrit dans la documentation internationale, est l'apparition asynchrone d'un cancer des viscères malgré l'absence de mutation du gène MSH2. Ce cas vient donc renforcer la nécessité d'avoir constamment à l'esprit la possibilité de SMT dans les cas de lésions sébacées dans la région périoculaire, et ce, indépendamment du test de dépistage de mutations.
Epidemiology of Sebaceous Carcinoma in Alberta, Canada, from 1988 to 2007
Authors: Kuzel Paul , Metelitsa Andrei I. , Dover Douglas C. , Salopek Thomas G. 
Published: January 2017

Background: The epidemiology of sebaceous carcinoma (SC) has not previously been examined in a Canadian population. Objective: To determine the epidemiologic trends of SC in Alberta, Canada, from 1988 to 2007. Methods: This study was a population-based, retrospective, epidemiologic analysis of SC in Alberta over a 20-year span. Results: Over the study period, the age-standardized SC incidence increased from 0.22 per 100,000 to 0.65 per 100,000. Sebaceous carcinoma is a cancer that predominantly affects the elderly (over 85% of cases were in persons 60 years or older). Interestingly, the face (37.7% of cases), not the eyelids (26.2% of cases), was the most frequently affected site overall. Gender-specific trends reflected a slight male predominance (1.4:1) and significant differences in anatomic distribution between the sexes. Conclusion: For unexplained reasons, there has been a threefold increase in SC incidence in Alberta over the last two decades. In addition, there are significant gender-specific differences in the anatomic distribution of SC. Contexte: L'épidémiologie du carcinome sébacé (CS) n'a jamais fait l'objet d'étude au Canada. Objectif: L'étude visait à déterminer les tendances épidémiologiques du CS en Alberta, au Canada, de 1988 à 2007. Méthodes: Il s'agit d'une analyse épidémiologique, rétrospective, fondée sur la population, du CS, en Alberta, sur une période de 20 ans. Résultats: Au cours de la période à l'étude, l'incidence du CS normalisée selon l'âge est passée de 0.22 pour 100,000 à 0.65 pour 100,000. Le carcinome sébacé est un cancer qui touche surtout les personnes âgées (plus de 85% des cas se comptaient parmi les personnes de 60 ans et plus). Point intéressant, la région le plus souvent touchée, dans l'ensemble, était la face (37.7% des cas), et non les paupières (26.2% des cas). Les tendances propres à chaque sexe ont révélé une fréquence légèrement plus élevée chez les hommes que chez les femmes (1.4/1) et des différences importantes entre les sexes quant à la répartition anatomique du siège des lésions. Conclusion: Pour des raisons inconnues, l'incidence du CS a triplé en Alberta au cours des deux dernières décennies. De plus, il existe des différences importantes entre les sexes quant à la répartition anatomique du CS.