Erratum: Retraction of the landmark glyphosate safety publication by Williams, Kroes and Munro (2000) should be reversed.
[This corrects the article on p. 1107 in vol. 25, PMID: 42517087.].
Biomedical subjects
Publications and source records attributed to Aristidis M Tsatsakis.
[This corrects the article on p. 1107 in vol. 25, PMID: 42517087.].
The decision by the co-Editor-in-Chief of Regulatory Toxicology and Pharmacology, Prof. Martin van den Berg, to retract the 2000 review article by Williams, Kroes, and Munro has elicited widespread criticism within the scientific community. Issued in late 2025, the retraction decision cites procedural concerns including potential ghostwriting, undisclosed conflicts of interest, and omission of certain unpublished studies, invoking Committee on Publication Ethics guidelines despite lacking evidence of fraud or scientific flaws. This editorial argues that the retraction decision involves editorial overreach and misapplication of the guidelines. The alleged omissions stemmed from proprietary data access limitations that were disclosed in the original paper. Subsequent reviews by several independent expert panels and regulatory authorities with access to all glyphosate data, including the studies cited by the retracting editor, reached similar conclusions. Claims of ghostwriting were previously investigated and found lacking, including a declaration by EFSA as to the clarity of the conflict disclosures. The retraction's timing, reliance on litigation documents, and apparent biases that were not disclosed in the retraction notice raise questions of ideological interference. Absent substantive rebuttals based on scientific merit rather than speculative claims of inappropriate authorship and data access, this retraction decision sets a dangerous precedent for retroactive censorship, potentially chilling beneficial industry-academic collaborations and eroding trust in the integrity of scientific publishing. With the strongest conviction, we assert that retracting a paper without scientific flaws isn't protection-it is censorship. We therefore call for the immediate reversal of this flawed and unjustified retraction to preserve trust in peer-reviewed literature.
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OBJECTIVES: Poor solubility and toxicity severely hinder the clinical use of amphotericin B (AmB), in spite of its attractive chemotherapeutic properties. Water-soluble complexes of AmB and polyvinylpyrrolidone (AmB-PVP) could display lower cytotoxicity while maintaining antifungal activity. METHODS: AmB-PVP [with PVP of 10, 24 and 40 kDa (AC1, AC2 and AC4)] were compared with free AmB for (i) activity against Candida spp. (five albicans; nine non-albicans) and Aspergillus spp. (four strains), (ii) haemolysis of sheep red blood cells, and (iii) release of lactate dehydrogenase from J774 macrophages [with further comparison with free PVP and a liposomal formulation of amphotericin (AmBisome)]. RESULTS: MICs and MFCs of AC1, AC2 and AC4 against Candida spp. and of AC2 and AC4 against Aspergillus spp. were similar to those of AmB (and even lower for some Candida strains). Killing kinetics (24 h) were also similar. Haemolytic activity of AC2 and AC4 was 2-fold lower than that of free AmB. Cytotoxicity of AC2 towards J774 macrophages was 8-fold lower, and that of AC4 5-fold lower than that of AmB and not significantly different from that of AmBisome. The lower cytotoxicity of AC2, AC4 was correlated with a lower cellular accumulation of amphotericin. Spectroscopic analysis shows that the lower toxicity of AmB-PVP was not owing to significant change in the monomeric/polymeric forms ratio of the drug. CONCLUSIONS: AmB-PVP complexes compared favourably with AmB for antifungal activity, were less haemolytic and cytotoxic than AmB, and show a similar cytotoxicity profile to AmBisome.
Lead is a metal which has been associated with human activities for the last 6000 years. In ancient civilizations, uses of lead included the manufacture of kitchen utensils, trays, and other decorative articles. However, lead is also toxic to humans, with the most deleterious effects on the hemopoietic, nervous, reproductive systems and the urinary tract. The main sources of lead exposure are paints, water, food, dust, soil, kitchen utensils, and leaded gasoline. The majority of cases of lead poisoning are due to oral ingestion and absorption through the gut. Lead poisoning in adults occurs more frequently during exposure in the workplace and primarily involves the central nervous system. Symptoms of hemopoietic system involvement include microcytic, hypochromic anemia with basophilic stippling of the erythrocytes. Hyperactivity, anorexia, decreased play activity, low intelligence quotient, and poor school performance have been observed in children with high lead levels. Lead crosses the placenta during pregnancy and has been associated with intrauterine death, prematurity, and low birth weight. In 1991, the Centers for Disease Control and Prevention in the USA redefined elevated blood lead levels as those > or = 10 microg/dl and recommended a new set of guidelines for the treatment of lead levels > or =15 microg/dl.
BACKGROUND: In Crete, the largest island of Greece, many pesticide formulations are increasingly used in agriculture in order to raise crop production. This study reviews a number of pesticide poisoning cases registered at the Center of Toxicology and Forensic Sciences Research at the University of Crete between 1991 and 2001. MATERIAL/METHODS: The medical records and toxicological data of the pesticide poisonings are presented. The analyzed samples were mainly blood and/or urine, but also gastric fluids and other tissues. Analysis involved a variety of techniques. RESULTS: Eleven poisonings caused by paraquat (7 men, 4 women, aged 15-58 years) are reported, five of which had fatal outcome. Initial paraquat plasma levels ranged between 0.4-165 pg/ml. Thirteen intoxications due to various organophosphorous agents are presented (11 men, 2 women, aged 13-69 years). Pesticide blood levels upon admission ranged from 1.0-108 pg/ml and there were six fatalities. Carbamate poisonings (4 men, 2 women, aged 32-60 years) were caused by methomyl (initial blood levels 1.6-57 mg/l) and resulted in death. A case of methyl bromide intoxication is also presented. CONCLUSIONS: The results of the study highlight the toxic and potentially lethal effects of pesticide formulations used in agriculture. Special seminars should be run to educate farmers on the proper use of these agents and the supply of pesticides should be restricted to those who follow all safety measures. Physicians should be trained to promptly identify and treat pesticide intoxications.
This is a report of a 12-year-old epileptic child undergoing chronic treatment with carbamazepine who was found comatose. He was considered to have acute severe drug toxicity. Measurement of carbamazepine concentration in the patient's hair segments together with the carbamazepine blood levels were both important in determining the chronic nature of the patient's intoxication.
The main purpose of the present study was to determine whether hair analysis would be a suitable method to assess chronic exposure of rabbits to the pesticide diazinon. A controlled study was designed, in which white rabbits of the New Zealand variety were systemically exposed to two dosage levels (15 mg/kg per day and 8 mg/kg per day) of the pesticide, through their drinking water, for a period of 4 months. Hair samples from the back of the rabbits were removed before commencing the experiment and at the end of the dosing period. Parallel experiments with spiked hair were carried out in order to design a simple and efficient method of extraction of diazinon from hair. The hair was pulverized in a ball mill homogenizer, incubated in methanol at 37 degrees C overnight, liquid-liquid extracted with ethyl acetate and measured by chromatography techniques (GC-NPD and GC-MS) for confirmation. The concentration of the diazinon in the hair of the exposed animals ranged from 0.11 to 0.26 ng/mg hair. It was concluded that there is a relationship between the administered dose and the detected pesticide concentration in hair. Finally, it seems that hair analysis may be used to investigate chronic exposure to the pesticide.
BACKGROUND: Cathepsin B, a lysosomal cysteine protease, has a major role in the mechanisms of tumor metastasis. The aim of the present work was to examine the correlation between cathepsin B activity and the metastatic potential of human pancreatic cancer. METHODS: The primary cell line COLO 357 and the derivative tumor cell lines FG, L3.1, L3.2, L3.3, L3.4, and L3.5, which are characterized by progressively increasing metastatic potential, were injected intrasplenically in the athymic mice. Cathepsin B activity, metastasis, and ultrastructural characteristics were assessed. RESULTS: An increased number of liver tumor nodules was observed with each subsequent intrasplenic inoculation (p = 0.001), associated with lymph node, splenic, and pancreatic involvement. Cathepsin B activity progressively increased (p = 0.001) and was strongly positively correlated with the metastatic potential. However, no correlation was found between the metastatic potential and ultrastructural characteristics. CONCLUSIONS: These findings further support the central role of cathepsin B in metastasis in a combined in vitro/in vivo model.
Fluorescence polarization immunoassay (FPIA) is a convenient homogeneous assay, the use of which is restricted in environmental analysis by low sensitivity and matrix effects. We selected the herbicides 2,4D and 2,4,5T to synthesize new L-lysine-based fluorescent tracers using solid-phase chemistry. In addition, three different immunogens of 2,4,5T were prepared for immunization and antibody production. The new tracers and antibodies were adapted to FPIA. Tracers with the hapten attached to the alpha-aminogroup of L-lysine and fluorescein to the e-amino group exhibited at least a 5-fold increased sensitivity when compared to the previously reported ethylenediamine-based tracer (2,4D-EDA-F). The isomeric structure (hapten attached to the e-amino and fluorescein to the alpha-amino group) appeared 7.6 times less sensitive, and all other alternative structures exhibited even lower sensitivities. This observation was confirmed against the monoclonal anti-2,4D antibody E2/G2 and polyclonal anti-2,4,5T antibodies. The affinity constant of 2,4D-EDA-F with E2/G2 was 8.1 times higher when compared with the new tracer, suggesting the more specific nature of the L-lysine-based tracer, the use of which leads to a more sensitive assay. This type of tracer could improve performance and lower substantially the detection limits of FPIAs.
Hair analysis was used for the assessment of exposure to organochlorine pollutants in specimens from Greece, Romania and Belgium. A simple method (using 3 N HCI as incubation reagent, liquid-liquid extraction with hexane/ dichloromethane (DCM), alumina/acid silica clean-up and GC-ECD/GC-MS analysis) was used for screening of specimens. The highest organochlorine load (up to 148 ng/g hair for the sum of PCB, DDT and hexachlorocyclohexane (HCH) isomers) was found in samples from a group of Greek women with past occupational exposure to pesticides. DDTs were the main organochlorine pollutants in Greek samples (up to 70%), while in Belgian hair samples their contribution was reduced to 40%. PCB mean concentration was higher in Belgian specimens (up to 14 ng/g hair). Lindane (y-HCH) was the main HCH isomer found in the samples (up to 82% in the Greek samples). Contribution of p,p'-DDT to the sum of DDTs was higher in Greek samples and indicates recent exposure to technical DDT. Similar PCB 153/sum PCBs ratios were found for each of the three countries suggesting similar sources of pollution with PCBs (mainly dietary). Artificially coloured hair samples were found to have lower, but not statistically significant concentrations of organochlorine pollutants than the non-coloured hair.
BACKGROUND: Arachidonic acid metabolites known to affect platelet function also interfere with tumor growth and metastases. The purpose of this study was to evaluate the anti-metastatic potential of ketoconazole, a thromboxane synthetase and 5-lipoxygenase inhibitor, on hepatic metastasis from a human pancreatic adenocarcinoma in nude mice and its effect on serum prostaglandin levels. METHODS: The human pancreatic tumor cells (RWP-2) were injected intrasplenically in nude mice grouped into control, ketoconazole (270 microg), ketoconazole (360 microg), and ketoconazole (540 microg). The agent was administered intraperitoneally 30 min before and every 24 h after the tumor cell inoculation for 8 days. In a separate experiment thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2) and 6-Keto-F1a (stable prostacyclin derivative) were measured on blood from controls, tumor bearing animals and animals bearing tumors treated with 270 microg of ketoconazole. RESULTS: Statistically significant differences were observed between the control and three-treatment groups on the reduction of liver tumor nodules (p < 0.001), and in the liver surface areas occupied by tumor (p < 0.001). The TxB2 levels decreased from 150.6 ng/mL in the tumor bearing to 104.8 ng/mL in the ketoconazole treated animals (p < 0.05). PGD2, PGE2 and 6-keto-F1a levels increased to 7.1 ng/mL, 8.3 ng/mL, and 13.6 ng/mL from 3 ng/mL, 5.8 ng/mL, and 0.02 ng/mL respectively (p < 0.001). CONCLUSIONS: These results indicate that ketoconazole significantly reduced hepatic metastases from the human pancreatic carcinoma RWP-2 in the nude mouse model, and inhibited thromboxane B2 formation, potentiating a concomitant redirection of platelet endoperoxide metabolism into PGD2, PGE2, and 6-keto-F1a. It is hypothesized that the changes in the arachidonic acid metabolism mediate the ameliorating effect of ketoconazole on experimental hepatic metastasis.
The present study aimed to improve the gas chromatography-mass spectrometry (GC-MS) method, already developed in our laboratory, for trace analysis of diazinon in hair. Furthermore, it aimed to compare the disposition of the pesticide in the hair of two different animal species, one susceptible to diazinon toxicity and one resistant, under identical experimental conditions. Sprague Dawley rats were systemically exposed to two dose levels (6 mg/kg/day and 3 mg/kg/day) of the pesticide, through their drinking water, for a period of one and a half months. Hair samples from the back of the rats were removed before commencing the experiment and at the end of the dosing period. Diazinon was selectively isolated from pulverized hair, sample or spiked, by stepwise consequent extractions with methanol and ethyl acetate and quantified by GC-negative chemical ionization-MS. It was found that the concentration of diazinon in the hair of exposed animals was dose dependent and was found to be 0.24 +/- 0.01 ng/mg (n = 5) and 0.53 +/- 0.05 ng/mg (n = 5) for the low and high dosage, respectively. The concentration in both dose groups was much higher than the corresponding rabbit hair (rabbits were exposed to the pesticide under similar experimental conditions) as previously reported. Our results strongly point to the possibility of using hair analysis for low-level exposure monitoring of diazinon.
The soy isoflavone genistein is a phytochemical which can affect the proliferation of both normal and cancer cells. The specific inhibition of protein tyrosine kinase (PTK) by which it effects the proliferation of cancer cells is a well-known mechanism of its action. Glycosaminoglycans (GAGs)/proteoglycans (PGs) are considered to be of great importance in the development and progression of cancer. The synthesis of GAGs by two osteosarcoma cell lines, MG-63 and SAOS-2, which differ in the density of estrogen receptors (ER) they express, and the effects of genistein on their synthesis and distribution among culture medium and cell membrane were studied. The obtained results showed that both cell lines synthesized extracellular hyaluronan (HA) and both extracellular and cell-associated galactosaminoglycans (GalAGs) and heparan sulfate (HS). Even though both cell lines synthesized considerable amounts of PGs, the SAOS-2 cells produced HA, GalAGs and HS at considerably lower rates than the MG-63 cells. The inhibitory effect of genistein on the synthesis of both extracellularly secreted and cell-associated GAGs/PGs in SAOS-2 2 cells was found to be dose-dependent and mediated most probably by a PTK mechanism. The synthesis of GAGs/PGs by the MG-63 cells in the presence of genistein was dependent on their type and localization, suggesting that a more complex mechanism regulates the PG synthesis. This may well involve the effect of genistein via the estrogen receptors, which are present in much higher density in MG-63 cells as compared to SAOS-2 cells.