2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases

A recent study showed that tetrahydrofuran (THF), a widely used solvent, is carcinogenic in experimental animals. Despite its carcinogenic activity, there is a paucity of information regarding cellular toxicity, biomolecular damage, and genotoxicity induced by THF. We describe here the structural characterization of adducts produced by the reaction of oxidized THF with 2'-deoxyguanosine (dGuo-THF 1 and dGuo-THF 2), 2'-deoxyadenosine (dAdo-THF), and 2'-deoxycytidine (dCyd-THF). Adducts were isolated from in vitro reactions by reverse-phase HPLC and fully characterized on the basis of spectroscopic measurements. The stable derivatives obtained by the reduction of adducts with NaBH(4) (the case of dGuo-THF 1, dCyd-THF, and dAdo-THF) and the stable adduct dGuo-THF 2 were used as standards for optimization of chromatographic separations for adduct detection in DNA through HPLC/ESI/MS-MS. Using this methodology, we successfully detected the four adducts in calf thymus DNA reacted with oxidized THF. The present study also provides evidence that rat liver microsomal monooxigenases oxidize THF to the reactive electrophilic compounds that are able to damage the DNA molecule, as indicated by a significant increase in adduct dGuo-THF 1 level when NADPH was added to the THF/microsomes/dGuo incubation mixtures. Our data point to DNA-THF adducts as possible contributing factors to the toxicological effects of THF exposure.     

Primary chemotherapy with sequential docetaxel followed by docetaxel and epirubicin in large operable breast cancer

Primary chemotherapy is increasingly used in patients with large operable breast cancer. Docetaxel and epirubicin are the most active agents in breast cancer treatment. PURPOSE: To evaluate clinical response rate, breast conserving surgery and pathological response rate in patients with large operable breast cancer treated with docetaxel followed by docetaxel and epirubicin as primary chemotherapy. PATIENTS AND METHODS: Patients with operable breast cancer more than 3 cm in the longest diameter with T2N0, T2N1 and T3N0 disease were enrolled. Patients were treated with three cycles of docetaxel 100 mg/m2 followed by three cycles of docetaxel 75 mg/m2 and epirubicin 90 mg/m2 prior to surgery. RESULTS: Sixty-five patients were enrolled between 09/2002 and 12/2005. The median age was 48.9 years and 72.3% were premenopausal. Median tumour size was 4.26 cm, 10.8% were T3 tumours and 38.5% had clinical positive lymph nodes. Of the tumours 58.5% were grade 1/2, 33.9% ER positive and 21.5% c-erb negative. All six cycles were administered to 62 patients; six cycles were delayed and five had dose reductions. Complete clinical response occurred in 41.5% of patients and partial response in 49.2%. Breast conserving surgery was performed in 30% of patients however it was feasible in 57%. Complete pathological response occurred in both primary tumour and nodes in 28%, and in 34% just in the primary tumour. Nine percent of cases had neutropenia and 7.7% febrile neutropenia, and two cases had a hypersensitivity reaction to docetaxel. One associated treatment death occurred. CONCLUSION: Docetaxel followed by epirubicin and docetaxel as primary chemotherapy results in a high clinical and pathological response rate. The majority of adverse events were predictable and manageable.     

Height‐based equations as screening tools for high blood pressure in pediatric practice,the GENOBOX study

Due to the absence of easily applicable cut‐off points to determine high blood pressure or hypertension in children, as in the adult population, blood pressure is rarely measured in the pediatrician''s clinical routine. This has led to an underdiagnosis of high blood pressure or hypertension in children. For this reason, the present study evaluate the utility of five equations for the screening of high blood pressure in children: blood pressure to height ratio, modified blood pressure to height ratio, new modified blood pressure to height ratio, new simple formula and height‐based equations. The authors evaluated 1599 children between 5 and 18 years. The performance of the five equations was analyzed using the receiver‐operating characteristics curves for identifying blood pressure above P90th according to the American Academy of Pediatrics Clinical Practice Guideline 2017. All equations showed an area under the curve above 0.882. The new modified blood pressure to height ratio revealed a high sensitivity whereas the height‐based equations showed the best performance, with a positive predictive value above 88.2%. Finally, all equations showed higher positive predictive values in children with overweight or obesity. The height‐based equation obtained the highest PPV values above 71.1% in children with normal weight and above 90.2% in children with overweight or obesity. In conclusions, the authors recommend the use of the height‐based equations equation because it showed the best positive predictive values to identify children with elevated blood pressure, independently of their sex, pubertal and weight status.     

Characterization of Leishmania species from Peru

Twenty-six isolates of Leishmania parasites of Peruvian origin were studied by isoenzyme electrophoresis of four marker enzymes (ASAT, ALAT, G6PD and GPI), kinetoplast DNA hybridization and monoclonal antibody binding and compared with marker strains of the New World organisms L. b. braziliensis, L. b. guyanensis, L. m. mexicana and L. m. amazonensis. 12 of the isolates studied were of Andean origin; 11 of these were isolated from patients with Andean cutaneous leishmaniasis. The organisms originating from the Peruvian Amazonian forest were isolated from patients with cutaneous (12 cases) or mucocutaneous (2 cases) leishmaniasis. One of the Andean isolates was obtained from an infected phlebotomine vector. 25 of the new isolates were identified as L. braziliensis ssp. according to the three techniques employed. The results of monoclonal antibody binding showed that 23 of the isolates were indistinguishable from L. b. braziliensis. Two isolates identified as L. braziliensis ssp. according to their isoenzyme profiles and k-DNA hybridization patterns could not be classified at the subspecies level. The isolate obtained from the phlebotomine vector could not be identified. No evidence of the existence of parasites of the L. mexicana complex in Peruvian territory was found in this study. The results obtained show a remarkable similarity between Leishmania of Andean origin and L. b. braziliensis.     

A new heparin fragment decreases liver ischemia-reperfusion injury

<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca²⁺,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],     

Assistive technology for communication of older adults: a systematic review

Objective: Describe the use of assistive technology to enhance communication opportunities for older adults.

Methods: A systematic review was conducted in two databases, PubMed and Web of Science, by using two different searches in each. The search was limited to original articles, in English language, including people aged 60 years and older that used any type of assistive technology for communication. The articles found in the initial search were filtered by title, abstracts and the remaining articles were fully read.

Results: Eighteen studies were included in this review after the reading of full-texts. Most of the studies included apparently healthy participants with communication limitations due to aging related changes and the others included people with some pathology that prevent them from normal communication.

Conclusion: Four categories of assistive technology were identified: assistive technology for people with speech problems; robot or videoconferencing systems; Information and Communication Technologies and, other types of assistive technology for communication, such as hearing aids and scrapbooks. Assistive technology for communication of older adults is not only used by people with disabilities that prevent them from usual communication. They are mostly for older adults without a pathological communication problem.     

Frailty and vulnerability: Are the two terms equivalent in paediatrics and geriatrics?

The recent medical literature has been using the term vulnerability to refer to harm to human integrity. The concept is multifaceted. Bioethics researchers conceive vulnerability as one of the basic anthropological features of the human condition. On the other hand, some bioethics scholars advocate using the terms susceptibility or variable vulnerability to refer to diseased or destitute populations. Also, frailty and variable vulnerability are correlated but not equivalent conditions which have been described somehow interchangeably in the recent medical literature, especially in the study of the ageing phenomena. The extremes of age are especially vulnerable periods of life and there has been growing evidence that neonatal and early life events have long-term influence on both the ageing process and frailty. This paper discusses some issues relevant to vulnerability and frailty and how one could possibly distinguish between them. There is still much to be learned about how frailty and variable vulnerability affect the ageing process across the life span.