Konstantinos M. Kasiotis

Pesticide residues in honeybees, honey and bee pollen by LC–MS/MS screening: Reported death incidents in honeybees

The aim of this study was to investigate reported cases of honeybee death incidents with regard to the potential interrelation to the exposure to pesticides. Thus honeybee, bee pollen and honey samples from different areas of Greece were analyzed for the presence of pesticide residues. In this context an LC-ESI-MS/MS multiresidue method of total 115 analytes of different chemical classes such as neonicotinoids, organophosphates, triazoles, carbamates, dicarboximides and dinitroanilines in honeybee bodies, honey and bee pollen was developed and validated. The method presents good linearity over the ranges assayed with correlation coefficient values r(2)≥0.99, recoveries ranging for all matrices from 59 to 117% and precision (RSD%) values ranging from 4 to 27%. LOD and LOQ values ranged - for honeybees, honey and bee pollen - from 0.03 to 23.3 ng/g matrix weight and 0.1 up to 78 ng/g matrix weight, respectively. Therefore this method is sufficient to act as a monitoring tool for the determination of pesticide residues in cases of suspected honeybee poisoning incidents. From the analysis of the samples the presence of 14 active substances was observed in all matrices with concentrations ranging for honeybees from 0.3 to 81.5 ng/g, for bee pollen from 6.1 to 1273 ng/g and for honey one sample was positive to carbendazim at 1.6 ng/g. The latter confirmed the presence of such type of compounds in honeybee body and apicultural products.

Resveratrol and related stilbenes: their anti-aging and anti-angiogenic properties.

Dietary stilbenes comprise a class of natural compounds that display significant biological activities of medicinal interest. Among them, their antioxidant, anti-aging and anti-angiogenesic properties are well established and subjects of numerous research endeavors. This mini-review aspires to account and present the literature reports published on research concerning various natural and synthetic stilbenes, such as trans-resveratrol. Special focus was given to most recent research findings, while the mechanisms underlying their anti-aging and anti-angiogenic effects as well as the respective signaling pathways involved were also presented and discussed.

Novel pyrazole derivatives: Synthesis and evaluation of anti-angiogenic activity

The synthesis of a series of novel trisubstituted pyrazole derivatives and their PIFA-mediated conversion to molecules bearing the fused pyrazolo[4,3-c]quinoline ring system is reported. The anti-angiogenic activity of these compounds was evaluated by using in vitro assays for endothelial cell proliferation and migration, and in the chicken chorioallantoic membrane (CAM) assay. Compounds containing the fused pyrazolo[4,3-c]quinoline motifs emerged as potent anti-angiogenic compounds, which also had the ability to inhibit the growth of human breast (MCF-7) and cervical (Hela) carcinoma cells in vitro.

Synthesis and biological evaluation of novel daunorubicin-estrogen conjugates.

The synthesis of two novel daunorubicin-estrogen conjugates with a steroidal and a non-steroidal ligand was undertaken in an attempt to target the cytotoxicity of anthracycline to estrogen-receptor positive cells. These conjugates (3 and 4), in contrast to their corresponding ligands, displayed weak binding affinities of 0.079 and 0.851 for the estrogen receptor. Conjugate 3 was consistently more cytotoxic than 4, which however showed some selectivity to estrogen receptor positive cell lines.

Pyrazoles as potential anti-angiogenesis agents: a contemporary overview

Angiogenesis is a mulit-step process by which new blood vessels are formed from preexisting vasculature. It is a key rate limiting factor in tumor growth since new blood vessels are necessary to increase tumor size. In this context it has been shown that anti-angiogenic factors can be used in cancer therapy. Among the plethora of heterocyclic compounds administered as anti-angiogenesis agents, pyrazoles constitute one of the bottlenecks of this category. Currently, several pyrazole based compounds are administered or are in Phase II and III trials and new targets emerge. It is highly possible that the advent of the next two decades will lead to the discovery and use of additional pyrazoles whose anti-angiogenic profile will position them in the forefront of the battle of various malignancies. The present review is an attempt to focus on those pyrazoles that arise as anti-angiogenesis agents commenting both on the chemistry and bioactivity that these exhibit aiming to contribute to the perspectives that they hold for future research.

Determination of operator exposure levels to insecticide during bait applications in olive trees: Study of coverall performance and duration of application

In this study the operator exposure levels during bait applications of an insecticide in olive groves were determined using a whole body dosimetry method for dermal exposure. The study design allowed the roles of application task duration and coverall type to be evaluated as factors influencing operator exposure. Twenty applications were carried out with knapsack sprayers in the Tanagra region of Viotia, Greece, ten of which were for a 1h and ten for a 3h duration. An in-house GC-NPD analytical method was developed and validated for the determination of malathion, the active substance (a.s.) of the insecticide formulation used in field trials. The mean recovery of field-fortified samples was 84% (%RSD=3.0). Field trial results generally indicated lower operator exposure levels than indicated by the most relevant operator exposure predictive model. Residues of malathion on internal dosimeters were compared to those measured on the respective outer coveralls (potential dermal exposure) to evaluate the protective factor of each one of the two coverall types used. Both coverall types provided satisfactory levels of protection and can be considered as suitable protection for the conditions of the application scenario studied. Furthermore, the results indicated that there is not a strong correlation between exposure levels and duration of application.

Synthesis of Novel Nitro-substituted Triaryl Pyrazole Derivatives as Potential Estrogen Receptor Ligands

Novel tetrasubstituted pyrazole derivatives bearing a nitro substituent on their A-phenol ring were synthesized and their binding affinity towards the estrogen receptor (ER) subtypes ERalpha and ERbeta was determined. Among compounds tested, the 2-nitrophenol derivative 5c was found to bind satisfactorily to both estrogen receptor subtypes (RBAalpha=5.17 and RBAbeta=3.27). In general, the introduction of a nitro group into the A ring of these compounds was found to benefit their ERbeta binding abilities.

Dermal & inhalation exposure of operators during fungicide application in vineyards. Evaluation of coverall performance.

In the present study the dermal and the inhalation exposure of five operators during fungicide applications in vineyards were determined. The produced exposure datasets can be used as surrogate for the estimation of the actual and the potential dermal as well as inhalation operator exposure levels for this application scenario. The dermal exposure was measured using the whole body dosimetry method while the inhalation exposure with the use of personal air sampling devices with XAD tubes located on the operators breathing zone. Ten field trials were carried out by 5 different operators using a tractor assisted hand-held lance with spray gun at the Tanagra region of Viotia, Greece. An in-house GC-ECD analytical method was developed and validated for the determination of penconazole, which was the active substance (a.s.) of the fungicide formulation used in field trials. The mean recovery of field-fortified samples was 81%. The operator exposure results showed expected variability and were compared to those derived from the German model for prediction of operator exposure. The comparison of the 75th percentile values for an operator wearing personal protection equipment has shown that the measured levels were 2.2 times lower than those estimated by the German model. The levels of actual dermal exposure ranged from 2 to 19 mg/kg a.s. applied. The protection provided by the two types of coveralls was evaluated and in comparison to the existing reduction factors used for other types of PPE (coveralls) was found satisfactory for the operator under the conditions of the specific applications.

Synthesis of (R)-dihydropyridones as key intermediates for an efficient access to piperidine alkaloids.

The efficient transformation of D-glucal to (2R)-hydroxymethyldihydropyridinone 5 in seven steps and 35 % overall yield is reported. Dihydropyridone 5 constitutes a versatile chiral building block for the synthesis of various piperidine alkaloids. In this regard, 5 was converted to piperidinol 13 and piperidinone 15, that may be further elaborated for the syntheses of (+)-desoxoprosophylline (1) and deoxymannojirimycin (3) or D-mannolactam (4), respectively.

Monitoring of systemic exposure to plant protection products and DNA damage in orchard workers

The systemic exposure of plum tree growers and operators to plant protection products (PPPs) and effects on DNA were assessed. Specifically, a GC-MS/MS method was developed and validated for the analysis of serum samples for the presence of seven active substances of PPPs. The analytical results verified the presence of myclobutanil, propargite, cypermethrin and deltamethrin in 7 out of 19 serum samples. The incidence of DNA damage was monitored using the single cell electrophoresis assay (comet assay). A paired Students t-test revealed a statistically significant increase of SSBs in the blood samples collected at the end of the cropping period as compared to the samples collected from the same subjects before the start of PPPs application period. Moreover, the group of seven subjects with detectable serum pesticides levels revealed statistically significant increase of SSBs as compared to the group of subjects with no detectable PPP levels. The results of the present study demonstrate that the agriculture workers may exhibit detectable level of systemic exposure to the applied PPPs which are correlated to increased DNA damage during the cultivation period.