Biochemical effects of comlex III Qo site respiratory chain inhibitor kresoxim-methyl on mammalian cells

The ultimate concern over pesticides in the environment is their toxic impact on nontarget organisms, including humans. For over the last two decades, the toxicological research has focused on pesticide-induced oxidative stress in terms of monitoring alterations in various biochemical and molecular compositions. A relative new group of agricultural fungicides, strobilurins, represent a major class of plant protection products and world's largest selling fungicides. They act as complex III Qo site inhibitors and thus disrupting electron transport in the respiratory chain. This electron leakage generates superoxide and potentially results in increased oxidative stress. The present study was aimed at investigating the biochemical mechanisms involved in the toxic action of kresoxim-methyl, a widely used agricultural fungicide of the stobilurins group on murine neuroblastoma cells (N2a)

Study of a cell-based electrochemical biosensor for fungicide cytotoxicity evaluation on mammalian cell lines

The ultimate concern over pesticides in the environment is their toxic impact on nontarget organisms, including humans. For over the last two decades, the toxicological research has focused on pesticide-induced oxidative stress in terms of monitoring alterations in various biochemical and molecular compositions. A relative new group of agricultural fungicides, strobilurins, represent a major class of plant protection products and world's largest selling fungicides. They act as complex III Qo site inhibitors and thus disrupt electron transport in the respiratory chain, which generates superoxide and potentially results in oxidative stress. Cell-based biosensors arise as powerful tools for the rapid detection of xenobiotics in food industries, agriculture and the environment. The present study was aimed at developing an electrochemical biosensor for cytotoxicity assays on mammalian cells, cultured on PEDOT electrodes. The cellular mono layers formed on top of the conductive material, support cell interactions, growth and metabolism as cells keep their original characteristics of morphology and functionality. In this framework, the action of kresoxim-methyl, of the stobilurins group, was examined on murine neuroblastoma cells (N2a). Square wave voltammetry (SWV) and a three-electrode configuration (W: PEDOT, C: Carbon, R: Silver) were used for recording the electrochemical changes after drug treatment. Moreover, standard viability/cytotoxicity protocols were conducted as references for assay comparisons. Due to PEDOTs transparent composition morphological observations and adhesion tests of the seeded cells were also made. Electrochemical responses against the fungicide provided evidence of the possible use of this assembly as a toxicity biosensor

High patient doses in interventional cardiology due to physicians' negligence: How can they be prevented?

Interventional cardiology procedures are usually associated with high patient doses and even deterministic radiation effects may occur. Expensive digital flat panels are preferably used to lower doses, and Athens General Hospital has recently installed one. However, this study shows that it is the cardiologists' practice that lowers patients' doses. Doses delivered to patients during two time periods (pre and after radiation protection training) on a total of 1196 coronary angiographies and 506 percutaneous transluminal coronary angioplasties were measured and analysed per cardiologist. Local reference levels (LRLs) were assessed and compared with the preliminary RLs provided by the European Research Program DIMOND. Results showed that although after the training patients' dose area product, fluoroscopy time, cumulative dose and number of images acquired were lowered, the situation remained unchanged for the cardiologist who delivered the highest doses. The question to answer next is how this bad practice can be prevented since no dose constraints apply to diagnostic or therapeutic procedures using ionising radiation. © The Author 2008. Published by Oxford University Press. All rights reserved

Anticancer and biochemical effects of Viscum album L. protein extracts on HeLa cells

European mistletoe (Viscum album) is a medicinal plant with significant anticancer properties. In vitro callus production provides an essential alternative for biomass production and medicinal compounds propagation. In this study, we investigated (a) the biotechnological production of somaclonal proteins from mistletoe callus propagation and (b) the in vitro cytotoxic properties of these mistletoe protein extracts against cervical cancer. Mistletoe proteins (MPEs) were extracted from natural resources (plant leaves and stems) and in vitro propagated variant calluses. Potential cytotoxic effects of the extracted proteins on HeLa cells were assessed by the MTT proliferation assay, whereas oxidative damage and induction of apoptosis were measured fluorometrically by the reactive oxygen species (ROS) sensitive carboxy-H2-DCFDA method and caspase-3 activation assays, respectively. Electrophoretic results indicated differences in the protein bands between callus and donor plant tissues. Leaf and stem protein extracts (PEs) demonstrated a strong impact on HeLa cells viability by promoting oxidative damage and inducing apoptosis in contrast to callus PEs. This study shows that MPEs application in HeLa cells causes oxidative alterations and apoptosis through caspase-3 activation and increased intracellular ROS levels. These findings may be useful for uncovering novel bioactive products of pharmaceutical interest as well as for gaining an understanding of the biochemical pathways of mistletoe proteins in cancer treatment. © 2019, Springer Nature B.V

Treatment of paediatric visceral leishmaniasis: amphotericin B or pentavalent antimony compounds?

Pentavalent antimony compounds and amphotericin B lipid formulations have been found highly active for the treatment of visceral leishmaniasis. This study focuses on which treatment is preferable in the best interests of the child. Records were reviewed of children in our hospital aged 0-14 years, diagnosed with visceral leishmaniasis, during the last 4 years. Twenty-nine children were identified. Ten were treated with meglumine antimonate (20 mg/kg/day for 21 days) and remained in hospital for 11-28 days (median 19 days), while 19 patients received liposomal amphotericin B at four different dosage schemes and were in hospital for 6-11 days (median 7 days). All of the patients were cured regardless of the treatment regime they followed. No relapses were noted. Liposomal amphotericin B would be preferable to meglumine antimonate if the reduction in hospital stay and hence the convenience of the patient balance the cost of medication. The optimal duration of treatment with liposomal amphotericin B remains to be determined. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved

Evaluation of potential medical and economic benefits of universal rotavirus vaccination in Greece

Aim: To evaluate the potential benefits of introducing universal rotavirus (RV) vaccination in Greece. Methods: A decision analytic model was developed to compare the burden and cost of rotavirus gastroenteritis (RVGE) with and without a universal RV vaccination (88% vaccination coverage) for a cohort of children followed from birth until the age of five. Results: Universal RV vaccination would substantially decrease the RVGE burden on the National Health System by reducing RVGE-related hospitalizations/emergency visits and medical consultations by 83% and 75%, respectively. Total RVGE-related costs was estimated at about 7.6 M€ and would be reduced by 5.9 M€ (-78%) if RV vaccination was introduced. A rapid effect is expected with 76% of cases and 84% of costs avoided would be averted within 2 years postvaccine introduction. The societal benefit would also be significant: total annual number of RVGE cases and parent's lost work days would be reduced by 67% and 78%, respectively. Including indirect costs, the total disease cost reduction would be 9 M€. Conclusion: Introduction of universal RV vaccination in Greece could offer considerable medical and economic benefits for the National Health System and society. Potential herd immunity would improve results in favour of vaccination. © 2011 The Author(s)/Acta Pædiatrica © 2011 Foundation Acta Pædiatrica

Trends in the epidemiology of childhood tuberculosis in Greece

SETTING: A hospital referral center for childhood tuberculosis (TB). OBJECTIVE: To evaluate the epidemiological and clinical features of childhood TB in the Greater Athens area in the last decade. DESIGN: We retrospectively reviewed the medical rec ords of patients aged <14 years treated for active TB between January 2000 and December 2009 at our pediatric TB clinic and compared the results with the patient turnover during the previous decade (1990-1999). Data concerning demographic and clinical characteristics were analyzed. RESULTS: A total of 321 children (median age 5.57 years, 157 males) with active TB were identified. About one third originated from areas where TB was previously recognized to be highly endemic. Twenty-three children (7%) had extra-pulmonary TB, and 61% of them originated from TB-endemic areas. Bacteriological confirmation was obtained in 40% of patients from whom specimens were obtained: 1 of 26 (3.8%) strains was multidrug-resistant. Most cases with drug-resistant Mycobacterium tuberculosis were noted among immigrant children. The average annual TB incidence was estimated at 5.37 per 100 000 for children aged <14 years in the Greater Athens area. Time trend analysis for the 20-year period revealed a significant reduction in the total number of TB cases (P = 0.002) and in TB among children from low-incidence countries (P < 0.0001). CONCLUSIONS: In our settings, active TB is decreasing among children of Greek origin; disease epidemiology and drug resistance is influenced by the increasing influx of immigrants from areas where the disease is highly prevalent. © 2012 The Union

Angiotensin-converting enzyme 2 (Ace2) as a novel biorecognition element in a cell-based biosensor for the ultra-rapid, ultra-sensitive detection of the sars-cov-2 s1 spike protein antigen

Antigen screening for the SARS-CoV-2 S1 spike protein is among the most promising tools for the mass monitoring of asymptomatic carriers of the virus, especially in limited resource environments. Herewith, we report on the possible use of the angiotensin-converting enzyme 2 (ACE2), the natural receptor and entry point of the virus, as a biorecognition element for the detection of the S1 antigen combined with an established bioelectric biosensor based on membrane-engineered cells. The working principle of our approach is based on the measurable change of the electric potential of membrane-engineered mammalian cells bearing ACE2 after attachment of the respective viral protein. We demonstrate that sensitive and selective detection of the S1 antigen is feasible in just three min, with a limit of detection of 20 fg/mL. In a preliminary clinical application, positive patient-derived samples were identified with a 87.9% score compared to RT-PCR. No cross-reactivity was observed against a wide range of nucleocapsid protein concentrations. The novel biosensor is embedded in a commercially ready-to-use testing platform, complete with the consumable immobi-lized cell–electrode interface and a portable read-out device operable through smartphone or tablet. In addition, the possible application of the system for the high throughput screening of potential pharmacological inhibitors of the ACE2 receptor-S1 RBD interaction is discussed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines

Crocus sativus L. has various pharmacological properties, known for over 3600 years. These properties are attributed mainly to biologically active substances, which belong to the terpenoid group and include crocins, picrocrocin and safranal. The aim of the current work was to examine the effects of crocins (CRCs) and their methyl ester derivate dimethylcrocetin (DMCRT) on glioblastoma and rhabdomyosarcoma cell lines, in terms of cytotoxicity and gene expression, implicated in proapoptotic and cell survival pathways. Cell cytotoxicity was assessed with Alamar Blue fluorescence assay after treatment with saffron carotenoids for 24, 48 and 72 h and concentrations ranging from 22.85 to 0.18 mg/mL for CRCs and 11.43 to 0.09 mg/mL for DMCRT. In addition, BAX, BID, BCL2, MYCN, SOD1, and GSTM1 gene expression was studied by qRT-PCR analysis. Both compounds demonstrated cytotoxic effects against glioblastoma and rhabdomyosarcoma cell lines, in a dose- and time-dependent manner. They induced apoptosis, via BAX and BID upregulation, MYCN and BCL-2, SOD1, GSTM1 downregulation. The current research denotes the possible anticancer properties of saffron carotenoids, which are considered safe phytochemicals, already tested in clinical trials for their health promoting properties