Search

Although there are alternative telomere structures, most telomeres contain DNA arrays of short repeats (6-26 bp) maintained by telomerase. Like other diptera, Chironomus riparius has noncanonical telomeres and three subfamilies, TsA, TsB and TsC, of longer sequences (176 bp) are found at their chromosomal ends. Reverse transcription PCR was used to show that different RNAs are transcribed from these sequences. Only one strand from TsA sequences seems to render a noncoding RNA (named CriTER- A); transcripts from both TsB strands were found ( CriTER- B and αCriTER- B) but no TsC transcripts were detected. Interestingly, these sequences showed a differential transcriptional response upon heat shock, and they were also differentially affected by inhibitors of RNA polymerase II and RNA polymerase III. A computer search for transcription factor binding sites revealed putative regulatory cis-elements within the transcribed sequence, reinforcing the experimental evidence which suggests that the telomeric repeat might function as a promoter. This work describes the telomeric transcriptome of an insect with non-telomerase telomeres, confirming the evolutionary conservation of telomere transcription. Our data reveal differences in the regulation of telomeric transcripts between control and stressful environmental conditions, supporting the idea that telomeric RNAs could have a relevant role in cellular metabolism in insect cells. [ABSTRACT FROM AUTHOR]

Objective: A study about the adherence of the antimicrobial prescriptions to the local guidelines of treatment of infections was conducted in a hospital emergency department to study the clinical and epidemiological characteristics of the patients who received these treatments. Conducting a feasibility study for supporting the design and execution of future studies, addressing specific aspects of the appropriateness of the antimicrobial prescription., Method: Observational, descriptive and cross-sectional pilot study, with retrospective data collection about the antimicrobial prescription in a hospital emergency department. Seven cross sections were made, corresponding to 7 different days of the week, in 7 consecutive weeks., Inclusion Criteria: patient over 14 years of age, with at least one first dose of antimicrobial treatment prescribed on the day of recruitment. The main variable was the inappropriate antimicrobial prescription according to the local guidelines. Epidemiological and clinical parameters of the patients were collected as secondary variables. In order to determine inappropriate prescription a revision was carried out by 2 specialists in emergencies, 2 pharmacists and one specialist in infectious diseases, all unrelated to prescriptions., Results: One hundred sixty eight patients with 192 prescriptions were evaluated. 76 (39.6%) of the prescriptions were not conformed to the local treatment guidelines. Of these, 55% were with active antimicrobial coverage against the microorganism but not recommended, 23.5% with inactive drugs, 13.7% presented an inappropriate dose and 7.8% were unnecessary treatment. The strength of agreement in the evaluation of the adequacy of treatment between doctors and pharmacists was high (kappa=0.71)., Conclusions: A high rate of inappropriate antimicrobial prescriptions was obtained in a hospital emergency department according to local guidelines. The hospital pharmacist has an opportunity to improve the use of antimicrobials in this area., (Copyright © 2022 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: A study about the adherence of the antimicrobial prescriptions to the local guidelines of treatment of infections was conducted in a hospital emergency department to study the clinical and epidemiological characteristics of the patients who received these treatments. Conducting a feasibility study for supporting the design and execution of future studies, addressing specific aspects of the appropriateness of the antimicrobial prescription., Method: Observational, descriptive and cross-sectional pilot study, with retrospective data collection about the antimicrobial prescription in a hospital emergency department. Seven cross sections were made, corresponding to seven different days of the week, in seven consecutive weeks., Inclusion Criteria: patient over 14 years of age, with at least one first dose of antimicrobial treatment prescribed on the day of recruitment. The main variable was the inappropriate antimicrobial prescription according to the local guidelines. Epidemiological and clinical parameters of the patients were collected as secondary variables. In order to determine inappropriate prescription a revision was carried out by two specialists in emergencies, two pharmacists and one specialist in infectious diseases, all unrelated to prescriptions., Results: 168 patients with 192 prescriptions were evaluated. Seventy-six (39.6%) of the prescriptions were not conformed to the local treatment guidelines. Of these, 55% were with active antimicrobial coverage against the microorganism but not recommended, 23.5% with inactive drugs, 13.7% presented an inappropriate dose and 7.8% were unnecessary treatment. The strength of agreement in the evaluation of the adequacy of treatment between doctors and pharmacists was high (kappa = 0.71)., Conclusions: A high rate of inappropriate antimicrobial prescriptions was obtained in a hospital emergency department according to local guidelines. The hospital pharmacist has an opportunity to improve the use of antimicrobials in this area., Competing Interests: Conflict of interest No conflict of interest has been reported., (Copyright © 2022 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Nelarabine is a purine analogue approved for the treatment of patients with T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukaemia (T-ALL) that have relapsed or are refractory to two previous chemotherapy regimens. Adverse reactions to nelarabine include neurological toxicity, the pathophysiological mechanisms of which are unknown, although the administration of intrathecal therapy at therapeutic doses given concomitantly with high-dose systemic chemotherapy that crosses the blood-brain barrier may potentiate neurotoxicity., Case Report: We report a case of a 29-year-old woman with a diagnosis of relapsed T-ALL who developed severe myelopathy and polyneuropathy of toxic origin that led to paraplegia, upper-limb paresis, and dysautonomia after the first cycle of nelarabine., Management and Outcome: Rehabilitation and pharmacological treatments were initiated early, but no evidence of a significant clinical change was obtained., Discussion: Neurotoxicity is a dose-dependent side effect of nelarabine. It is therefore important to consider previously administered neurotoxic drugs before using nelarabine and to monitor patients closely so as to be able to act promptly in case of toxicity. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered possible.

Objective: The Pharmacy and Therapeutics Committee is an advisory body to  the medical management of our hospital. Following Royal Decree 86/2015,  which regulates the Pharmacy and Therapeutics Committee of the Balearic  Islands, this committee prepared a technical report in which it assessed the  possible internal use of off-label drugs, drugs for compassionate use, and drugs  not included in the hospital's pharmacotherapeutic guide. The objective was to  analyse the clinical response achieved with the use of these drugs and their  associated costs., Method: Retrospective study of drugs whose use was requested from the  hospital's Pharmacy and Therapeutics Committee hospital between January and  December 2018. We analysed whether the requested treatment achieved the  objective established by the physician. The cost was calculated based on the  duration of the treatment until the objective was achieved or until treatment was discontinued., Results: In total, 70 requests were analysed: 59% achieved the expected therapeutic goal, 34% were considered to be therapeutic failures, and  7% were lost to follow-up. The overall cost of the 70 authorized treatments was  €1,140,240. The average cost per request was €16,288. Oncology and  Haematology services submitted more than 50% of the requests, and more than 75% of the budget was allocated to these medical services., Conclusions: More than half of the treatments analysed by the Pharmacy and  Therapeutics Committee of the hospital achieved their therapeutic goal, although the economic cost of their use was high., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P. acuta were evaluated at the molecular level by analysing changes in the transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), as well as in genes involved in the stress response, such as hsp70 and hsp90. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that BPA induced a significant increase in the mRNA levels of ER, ERR, and RXR, suggesting that these receptors could be involved in similar pathways or regulation events in the endocrine disruptor activity of this chemical at the molecular level in Gastropoda. Additionally, the hsp70 expression was upregulated after 5 and 72h of BPA exposures, but hsp90 was only upregulated after 5h of BPA exposure. Finally, we assessed the glutathione-S-transferase (GST) activity after BPA treatment and found that it was affected after 48h. In conclusion, these data provide, for the first time, evidences of molecular effects produced by BPA in the endocrine system of Gastropoda, supporting the potential of ER, ERR and RXR as biomarkers to analyse putative EDCs in ecotoxicological studies. Moreover, our results suggest that P. acuta is an appropriate sentinel organism to evaluate the effect of EDCs in the freshwater environment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Triclosan (TCS) is an antibacterial agent widely used in personal care and consumer products and commonly detected in aquatic ecosystems. In the present study, the effects of TCS on endocrine-related genes of Chironomus riparius aquatic larvae, a reference organism in aquatic toxicology, were evaluated. Twenty-four-hour in vivo exposures at 10µg/L, 100µg/L, and 1000µg/L TCS revealed that this xenobiotic was able to alter the transcriptional activity of ecdysone receptor gene (EcR), the ultraspiracle gene (usp), the estrogen-related receptor gene (ERR), and the E74 early ecdysone-inducible gene, as measured by real-time RT-PCR. Moreover, the hsp70 gene, a heat shock protein gene, was upregulated after exposure to TCS. The results of the present work provide the first evidence of the potential disruptive effects of TCS in endocrine-related genes suggesting a mode of action that mimics ecdysteroid hormones in insects., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental pollutant used worldwide as a plasticizer and solvent in many formulations. Based on available toxicological data, it has been classified as toxic for reproduction and as an endocrine disruptor. Despite this, ecotoxicological studies in aquatic wildlife organisms are still scarce. In the present work, the toxic molecular alterations caused by DEHP in aquatic larvae of the midge Chironomus riparius have been studied, by analyzing the transcriptional activity of genes related to some vital cellular pathways, such as the ribosomal machinery (rpL4, rpL13), the cell stress response (hsc70, hsp70, hsp40, hsp27), the ecdysone hormone pathway (EcR), the energy metabolism (GAPDH), and detoxication processes (CYP4G). Environmentally relevant concentrations (10-3 to 105 μg/L) and exposure conditions (24 to 96 h) have been tested, as well as the toxic effects after DEHP withdrawal. Although the compound caused no mortality, significant changes were detected in almost all the studied biomarkers: e.g. strong repression of hsp70; general inhibition of EcR; GAPDH activity loss in long exposures; among others. Our data show a general transcriptional downregulation that could be associated with an adaptive response to cell damage. Besides, the activity of the compound as an ecdysone antagonist and its delayed effects over almost all the biomarkers analyzed are described as novel toxic targets in insects., Competing Interests: The authors have declared that no competing interests exist.

The freshwater snail Physa acuta is a sensitive organism to xenobiotics that is appropriate for toxicity testing. Cadmium (Cd) is a heavy metal with known toxic effects on several organisms, which include endocrine disruption and activation of the cellular stress responses. There is scarce genomic information on P. acuta; hence, in this work, we identify several genes related to the hormonal system, the stress response and the detoxification system to evaluate the effects of Cd. The transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), the heat shock proteins genes hsp70 and hsp90 and a metallothionein (MT) gene was analysed in P. acuta exposed to Cd. In addition, the hsp70 and hsp90 genes were also evaluated after heat shock treatment. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that Cd presence induced a significant increase in the mRNA levels of ER, ERR and RXR, suggesting a putative mode of action that could explain the endocrine disruptor activity of this heavy metal at the molecular level on Gastropoda. Moreover, the hsp70 gene was upregulated after 24-h Cd treatment, but the hsp90 gene expression was not affected. In contrast, the hsp70 and hsp90 genes were strongly upregulated during heat shock response. Finally, the MT gene expression showed a non-significant variability after Cd exposure. In conclusion, this study provides, for the first time, information about the effects of Cd on the endocrine system of Gastropoda at the molecular level and offers new putative biomarker genes that could be useful in ecotoxicological studies, risk assessment and bioremediation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Organic ultraviolet (UV) filters are emerging contaminants that are ubiquitous in fresh and marine aquatic systems due to their extensive use in cosmetics, plastics, paints, textiles, and many other industrial products. The estrogenic effects of organic UV filters have been long demonstrated in vertebrates, and other hormonal activities may be altered, according to more recent reports. The impact of UV filters on the endocrine system of invertebrates is largely unknown. We have previously reported that some UV filters may affect ecdysone-related genes in the aquatic insect Chironomus riparius, an ecotoxicologically important model organism. To further analyze other possible effects on endocrine pathways, we first characterized four pivotal genes related with hormonal pathways in insects; thereafter, these genes were assessed for alterations in transcriptional activity after exposure to 4-methylbenzylidene camphor (4MBC) or benzophenone-3 (BP-3), two extensively used sunscreens. We found that both chemicals disturbed the expression of all four genes analyzed: hormonal receptor 38 (HR38), methoprene-tolerant (Met), membrane-associate progesterone receptor (MAPR) and insulin-like receptor (INSR), measured by changes in mRNA levels by real-time PCR. An upregulatory effect at the genomic level was detected in different developmental stages. Interestingly, embryos appeared to be more sensitive to the action of the UV filters than larvae. Our results suggest that the risk of disruption through different endocrine routes is not negligible, considering the significant effects of UV filters on key hormonal receptor and regulatory genes. Further effort is needed to develop environmental risk assessment studies on these pollutants, particularly for aquatic invertebrate model organisms., (Copyright © 2016 Elsevier Ltd. All rights reserved.)