The amnesic shellfish poison domoic acid enhances neurotoxicity by excitatory amino acids in cultured neurons

Summary A recent episode of human intoxication by cultured mussels containing a rare excitatory amino acid named domoic acid, received particular attention for its neurological implications. The intoxication produced neurological problems, such as headache, confusion, and loss of memory, particularly severe at times. Neuronal damage was found in the hippocampus and amygdala of four patients. We now report that in neuronal cultures the neurotoxicity of a domoic acid-containing mussel extract is the result of domoic acid potentiation of the excitotoxic effect of glutamic acid and aspartic acid present in high amounts in mussel tissue. Moreover, we show that subtoxic concentrations of domoic acid are sufficient to potentiate glutamic acid and aspartic acid neurotoxicity. We present evidence suggesting that the neurotoxic synergism may be due to a reduction of Mg^{+ +} block at the NMDA receptor-associated channel, following activation of NON-NMDA receptors by domoic acid.     

The concentrations of essential/toxic elements in serum of COVID-19 patients are not directly related to the severity of the disease

BackgroundIn recent months, the current COVID-19 pandemic has generated thousands of studies directly or indirectly related with this disease and/or the coronavirus SARS-CoV-2 causing the infection. On August 22, 2022, the database PUBMED included 287,639 publications containing the term COVID-19. However, in spite of the importance of trace elements in human health, including the immune system, data on the levels of metals/metalloids in COVID-19 patients is very limited.MethodsThe concentrations of As, Cd, Cr, Cu, Hg, Fe, Mg, Mn, Pb, Se, V and Zn were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in 126 serum samples of individuals infected with SARS-CoV-2, as well as in 88 samples of non-infected individuals. Participants were divided into four groups: i) individuals COVID-19 positive (COVID-19 +) with an asymptomatic infection course; ii) individuals suffering mild COVID-19; iii) individuals suffering severe COVID-19, and iv) individuals COVID-19 negative (COVID-19-) (control group). The occurrence of the analyzed metals/metalloids was evaluated along with the biochemical profile, including blood cell counts, lipids, proteins and crucial enzymes.ResultsSerum levels of Mg, V, Cr, Cu, Cd, and Pb were higher in COVID-19 positive patients than those in the control group. Although no significant differences were observed between the different groups of patients, the concentrations of Cd, Pb, V and Zn showed a tendency to be higher in individuals with severe COVID-19 than in those showing mild symptoms or being asymptomatic. Arsenic and Hg were rarely detected, regardless if the subjects were infected by SARS-CoV-2, or not. The current results did not show significant differences in the levels of the rest of analyzed elements according to the severity of the disease (asymptomatic, mild and severe).ConclusionsIn spite of the results here obtained, we highlight the need to reduce the exposure to Cd, Pb and V to minimize the potential adverse health outcomes after COVID-19 infection. On the other hand, although a protective role of essential elements was not found, Mg and Cu concentrations were higher in severe COVID-19 patients than in non-infected individuals.     

The effect of subminimal inhibitory concentrations of antibiotics on virulence factors expressed by Staphylococcus aureus biofilms

Aims: The effect of subminimal inhibitory concentrations (sub‐MICs) of cefalexin, ciprofloxacin and roxithromycin was investigated on some virulence factors [e.g. coagulase, Toxic Shock Syndrome Toxin 1 (TSST‐1) and biofilm formation] expressed by Staphylococcus aureus biofilms. Methods and Results: Biofilms were grown with and without the presence of 1/16 MIC of antibiotics on Sorbarod filters. Eluate supernatants were collected, and coagulase and TSST‐1 production were evaluated. Coagulase production was reduced in eluates exposed to roxithromycin when compared to control, while TSST‐1 production was reduced in biofilms exposed to cefalexin and to a lesser extent, ciprofloxacin. In addition, the ability of Staph. aureus to produce biofilm in microtitre plates in the presence of sub‐MIC antibiotics indicated that cefalexin induced biofilm formation at a wide range of sub‐MICs. TSST‐1 produced from the challenged and control biofilms was purified, and its proliferative activity was studied on single cell suspension of mouse splenocytes using MTS/PMS assay. No significant difference in the activity between the treated toxin and the control has been observed. Conclusions: Antibiotics at sub‐MIC levels interfere with bacterial biofilm virulence expression depending on the type and concentration of antibiotic used. Significance and Impact of the Study: The establishment of sub‐MICs of antibiotics in clinical situations may result in altered virulence states in pathogenic bacteria.     

Selected factors limiting the microbial degradation of recalcitrant compounds

Summary The focus of this review is to examine some of the reasons biodegradation may not take place in the environment even though its occurrence in the laboratory has been demonstrated. Some approaches for dealing with chemical persistence will be discussed. In addition, the potential of bioremediation as an in situ clean-up technology will be considered.     

三维适形放疗治疗食管鳞癌的近期疗效、生存率及预后的影响因素分析

目的:观察三维适形放疗治疗食管鳞癌的近期疗效、生存率并分析其预后的影响因素。方法:纳入我院从2010年11月～2016年10月收治的食管鳞癌患者150例进行研究,按治疗方式的不同分成研究组(n=84,三维适形放疗治疗)和常规组(n=66,常规放疗治疗)。随访3年,比较两组近期疗效、毒副反应发生情况以及3年生存情况。单因素分析研究组患者3年生存情况与性别、年龄、病变长度、病变部位、大体肿瘤体积(GTV)的关系,多因素Logistic回归分析三维适形放疗食管鳞癌患者预后的影响因素。结果:研究组治疗总有效率显著优于常规组(P0.05)。研究组放射性食管损伤、血液毒性反应发生率均显著低于常规组(均P0.05)。研究组1、2、3年存活率均显著高于常规组(均P0.05)。单因素Logistic分析结果显示:不同年龄、病变长度、病变部位以及GTV的食管鳞癌患者三年生存率比较差异有统计学意义(均P0.05)。多因素Logistic回归分析发现年龄≥70岁、病变长度≥50 mm、病变部位为胸下段、GTV≥40 cm3均是三维适形放疗食管鳞癌患者3年内死亡的危险因素。结论:三维适形放疗治疗食管鳞癌患者的近期疗效优于常规放疗,可降低毒副反应发生率,提高生存率。年龄≥70岁、病变长度≥50 mm、病变部位为胸下段、GTV≥40 cm~3均是三维适形放疗食管鳞癌患者3年内死亡的危险因素,值得临床重点关注。     

Study on the Interaction Mechanism of 2‐Aminoanthraquinone with Calf Thymus DNA

By utilizing multispectrosopic techniques, the toxic interaction of 2‐aminoanthraquinone (2‐AAQ) with calf thymus deoxyribonucleic acid (ctDNA) was investigated in vitro under simulated physiological conditions. The experimental results proved that 2‐AAQ has a toxic interaction with ctDNA. The binding capacity of DNA with 2‐AAQ is diminishing as the pH value of system increasing in the optimization of experimental condition. Moreover we selected pH 7.4, which is nearly physiological condition to enhance the practical significance. According to the Stern–Volmer equation, the quenching was the static quenching process. And the quenching constant can be derived from the fluorescence quenching spectrogram. Ultraviolet absorption spectra and the change in the fluorescence intensity at different ionic strengths further indicated that there was electrostatic binding between 2‐AAQ and ctDNA. The circular dichroism experiment showed that the DNA conformation varied from B to A conformation. The basic group enhanced after 2‐AAQ embedding. The double helix is more compact, and the DNA conformation changes. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:272‐278, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21487     

A novel method for cloning of coding sequences of highly toxic proteins

Background

During standard gene cloning, the recombinant protein appearing in bacteria as the result of expression leakage very often inhibits cell proliferation leading to blocking of the cloning procedure. Although different approaches can reduce transgene basal expression, the recombinant proteins, which even in trace amounts inhibit bacterial growth, can completely prevent the cloning process.

Genetic diversity and molecular detection of three toxic dinoflagellate genera (Alexandrium,Dinophysis, and Karenia) from French coasts

The objectives of this study were 1) to study the genetic diversity of the Alexandrium, Dinophysis and Karenia genera along the French coasts in order to design probes targeting specific DNA regions, and 2) to apply PCR-based detection to detect these three toxic dinoflagellate genera in natural samples. Genetic diversity of these toxic taxa was first studied from either cultures or cells isolated from Lugol-fixed field samples. By this way, partial sequences of the large ribosomal subunit (LSU rDNA) including the variable domains D1 and D2 of A. minutum, Alexandrium species inside the tamarensis complex, the D. acuminata complex and K. mikimotoi were obtained. Next, specific primers were designed for a selection of toxic algae and used during semi-nested PCR detection. This method was tested over a 3-month period on water samples from the Bay of Concarneau (Brittany, France) and on sediment from the Antifer harbor (The English Channel, France). Specificity and sensitivity of this molecular detection were evaluated using the occurrence of target taxa reported by the IFREMER (Institut Fran?ais de Recherche pour l'Exploitation de la Mer) monitoring network based on conventional microscopic examination. This work presents the first results obtained on the biogeographical distribution of genotypes of these three toxic genera along the French coasts.