Imperatorin interacts additively with novel antiseizure medications in the mouse maximal electroshock-induced seizure model: an isobolographic transformation.

BACKGROUND: Anticonvulsant effects of imperatorin (IMP) have been experimentally confirmed earlier, but no information is available on the interaction profiles of this naturally occurring coumarin when combined with novel antiseizure medication (ASMs). This study aimed to determine the effects of IMP on the anticonvulsant effects of lacosamide (LCM), oxcarbazepine (OXC), pregabalin (PGB), and topiramate (TPM) in the maximal electroshock-induced seizure (MES) model in mice. METHODS: The anticonvulsant effects exerted by novel ASMs (LCM, OXC, PGB, and TPM) when combined with constant doses of IMP (25 and 50 mg/kg) underwent isobolographic transformation to precisely classify the observed interactions in the mouse MES model. Total brain concentrations of ASMs were measured with high-pressure liquid chromatography to exclude the pharmacokinetic nature of interactions among IMP and the tested ASMs. RESULTS: IMP (50 mg/kg) significantly enhanced (p < 0.01) the anticonvulsant potency of LCM, OXC, PGB, and TPM in the mouse MES model. IMP (25 mg/kg) mildly potentiated the anticonvulsant action of LCM, OXC, PGB, and TPM, but no statistical significance was reported for these combinations. The isobolographic transformation of data from the MES test revealed that the interactions of novel ASMs with IMP were additive. Moreover, IMP (50 mg/kg) did not affect the total brain content of any of the novel ASMs in experimental mice. CONCLUSIONS: The additive interactions of IMP with LCM, OXC, PGB, and TPM in the mouse MES model accompanied by no pharmacokinetic changes in the total brain content of ASMs are worthy of recommendation for further studies.

Anticonvulsant effects of isopimpinellin and its interactions with classic antiseizure medications and borneol in the mouse tonic-clonic seizure model: an isobolographic transformation.

BACKGROUND: Overwhelming evidence indicates that some naturally occurring coumarins and terpenes are widely used in folk medicine due to their various therapeutic effects affecting the brain. Antiseizure medications (ASMs) are the principal treatment option for epilepsy patients, although some novel strategies based on naturally occurring substances are intensively investigated. This study was aimed at determining the influence of isopimpinellin (ISOP-a coumarin) when administered either separately or in combination with borneol (BOR-a monoterpenoid), on the antiseizure potencies of four classic ASMs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA)) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MATERIALS: Tonic-clonic seizures were evoked experimentally in mice after systemic (ip) administration of the respective doses of ISOP, BOR, and classic ASMs. Interactions for two-drug (ISOP + a classic ASM) and three-drug (ISOP + BOR + a classic ASM) mixtures were assessed isobolographically in the mouse MES model. RESULTS: ISOP (administered alone) had no impact on the anticonvulsant potencies of four classic ASMs. Due to the isobolographic transformation of data, the combination of ISOP + VPA exerted an antagonistic interaction, whereas the two-drug mixtures of ISOP + CBZ, ISOP + PHT, and ISOP + PB produced additive interactions in the mouse MES model. The three-drug combinations of ISOP + BOR with CBZ and PHT produced additive interactions, while the three-drug combinations of ISOP + BOR with PB and VPA exerted synergistic interactions in the mouse MES model. CONCLUSIONS: The most intriguing interaction was that for ISOP + VPA, for which the addition of BOR evoked a transition from antagonism to synergy in the mouse MES model.

Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model-An Isobolographic Transformation.

Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model.

Endocrine disrupting micropollutants in water and their effects on human fertility and fecundity.

INTRODUCTION AND OBJECTIVE: Micropollutants (MPs) are defined as persistent and biologically-active substances which occur in the environment in trace amounts, mainly as a result of industrial processes and human domestic activity. The published experimental data prove that, among other things, MPs present in the environment may also affect and disturb hormonal balance in humans, resulting in impairment of the reproductive function. In addition to the many MPs disrupting endocrine function described in literature and which exert an effect on human reproductive function, the study presents a review of current literature concerning the exposure to Bisphenol A, phthalates, organochlorine pesticides, and pyrethroids. REVIEW METHODS: Two independent authors searched in PubMed and Google scholar (any date until September 2022) for studies concerning chosen endocrine-disrupting MPs in water and their effects on human fertility and fecundity. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: The review of the literature showed that EDMs present in the environment may create risk in the prenatal and postnatal development following premature birth, and exert a negative effect on fertility and reproductive functions in humans, especially during the perinatal period. SUMMARY: The presented review of literature indicates a negative effect of exposure to BPA, phthalates, OC and OP pesticides, as well as to pyrethroids, regarding human reproductive health. It also demonstrated considerable differences according to gender. Generally, there is a definitely stronger evidence for the presence of a cause-effect relationship between the discussed EDMs and a decreased fertility and fecundity in males. The negative effect of exposure to Bisphenol A, phthalates, selected organochlorine pesticides and pyrethroids appears to be quite well documented.

Methodology for preparing a cosmetic sample for the development of Microorganism Detection System (SDM) software and artificial intelligence learning to recognize specific microbial species.

INTRODUCTION AND OBJECTIVE: The article presents the methodology of preparing a cosmetic sample for analysi, and the creation of a dataset for teaching artificial intelligence to recognize specific species of microorganisms in cosmetic samples in terms of compliance with the ISO standard document, to develop of the Microorganism Detection System (SDM). MATERIAL AND METHODS: Methodology of preparation a cosmetic sample for testing covers the steps from taking a cosmetic sample to obtaining separated living microorganisms through staining to photos, which in the final stage are used for analysis of the purity of cosmetics by SDM, as well as for learning and testing of the deep convolutional neural network (CNN) for detecting and classifying cells of specific species of bacteria, fungi and yeast in cosmetics, according to the document of standard PN-EN ISO 17516-2014:11. RESULTS: A new techique was devised for preparing a cosmetic sample for the development of Microorganism Detection System (SDM) software, and artificial intelligence learning to recognize specific microbial species. Based on metod demonstrated, the Intelligent algorithms of SDM proved to be effective in counting and recognizing specific microorganisms (average accuracy for Candida albicans - 97%, Escherichia coli - 76%, Pseudomonas aeruginosa - 70%, Staphylococcus aureus - 85%), which are the most important species for the assessment of the purity of cosmetics. In addition, the reproducibility of the developed method was verified, and the results obtained were comparable to the breeding methods currently used, based on specific standards. CONCLUSIONS: The experiments confirmed the high sensitivity and specificity of the SDM method, its repeatability and, above all, the comparability of the results with clasic methods of European standards.

The Microorganism Detection System (SDM) for microbiological control of cosmetic products.

The Microorganism Detection System (SDM) is a new solution using artificial intelligence, unique on the international scale, to correctly identify and count microorganisms, with particular emphasis on specificlisted microorganisms (Document of Standard PN-EN ISO 17516-2014:11) - Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus. SDM enables the use of algorithms for microscopic image interpretation in the microbiological assessment of the cosmetics in accordance with the standard, providing an answer to whether the tested product complies with the standard. Apart from the software part of SDM, an integral part of the system is an innovative methodology for preparing a cosmetic sample for testing. The experiments confirm the high sensitivity and specificity of the SDM method, its repeatability and, above all, the comparability of the results with the methods of European standards.

Interactions among Lacosamide and Second-Generation Antiepileptic Drugs in the Tonic-Clonic Seizure Model in Mice.

Combination therapy with two or three antiseizure medications (ASMs) is sometimes a preferred method of treatment in epilepsy patients. (1) Background: To detect the most beneficial combination among three ASMs, a screen test evaluating in vivo interactions with respect to their anticonvulsant properties, was conducted on albino Swiss mice; (2) Methods: Classification of interactions among lacosamide (LCM) and selected second-generation ASMs (lamotrigine (LTG), pregabalin (PGB), oxcarbazepine (OXC), and topiramate (TPM)) was based on the isobolographic analysis in the mouse maximal electroshock-induced seizure (MES) model. Interactions among LCM and second-generation ASMs were visualized using a polygonogram; (3) Results: In the mouse MES model, synergy was observed for the combinations of LCM + TPM + PGB and LCM + OXC + PGB. Additivity was reported for the other combinations tested i.e., LCM + LTG + TPM, LCM + LTG + PGB, LCM + LTG + OXC, and LCM + OXC + TPM in this seizure model. No adverse effects associated with triple ASM combinations, containing LCM and second-generation ASMs were observed in mice; (4) Conclusions: The combination of LCM + TPM + PGB was the most beneficial combination among the tested in this study, offering synergistic suppression of tonic-clonic seizures in mice subjected to the MES model. Both the isobolographic analysis and polygonogram method can be recommended for experimental epileptology when classifying interactions among the ASMs.

Polygonogram and isobolographic analysis of interactions between various novel antiepileptic drugs in the 6-Hz corneal stimulation-induced seizure model in mice.

Pharmacotherapy with two antiepileptic drugs in combination is usually prescribed to epilepsy patients with refractory seizures. The choice of antiepileptic drugs in combination should be based on synergistic cooperation of the drugs with respect to suppression of seizures. The selection of synergistic interactions between antiepileptic drugs is challenging issue for physicians, especially, if 25 antiepileptic drugs are currently available and approved to treat epilepsy patients. The aim of this study was to determine all possible interactions among 5 second-generation antiepileptic drugs (gabapentin (GBP), lacosamide (LCM), levetiracetam (LEV), pregabalin (PGB) and retigabine (RTG)) in the 6-Hz corneal stimulation-induced seizure model in adult male albino Swiss mice. The anticonvulsant effects of 10 various two-drug combinations of antiepileptic drugs were evaluated with type I isobolographic analysis associated with graphical presentation of polygonogram to visualize the types of interactions. Isobolographic analysis revealed that 7 two-drug combinations of LEV+RTG, LEV+LCM, GBP+RTG, PGB+LEV, GBP+LEV, PGB+RTG, PGB+LCM were synergistic in the 6-Hz corneal stimulation-induced seizure model in mice. The additive interaction was observed for the combinations of GBP+LCM, GBP+PGB, and RTG+LCM in this seizure model in mice. The most beneficial combination, offering the highest level of synergistic suppression of seizures in mice was that of LEV+RTG, whereas the most additive combination that protected the animals from seizures was that reporting additivity for RTG+LCM. The strength of interaction for two-drug combinations can be arranged from the synergistic to the additive, as follows: LEV+RTG > LEV+LCM > GBP+RTG > PGB+LEV > GBP+LEV > PGB+RTG > PGB+LCM > GBP+LCM > GBP+PGB > RTG+LCM.

Sub-additive (antagonistic) interaction of lacosamide with lamotrigine and valproate in the maximal electroshock-induced seizure model in mice: an isobolographic analysis.

BACKGROUND: Launching polytherapy with two or three antiseizure drugs (ASDs) in patients with epilepsy is still problematic. The choice of ASDs to combine them together is usually based on clinicians' experience and it requires knowledge about mechanisms of action of the studied ASDs and their drug-drug interactions, whose nature may be favorable, neutral or unfavorable. To characterize three-drug interaction among lacosamide (LCM), lamotrigine (LTG) and valproate (VPA), the type I isobolographic analysis was used. The antiseizure effects of three-drug combination were analyzed in a model of maximal electroshock-induced seizures (MES) in albino Swiss mice. MATERIALS AND METHODS: The seizure activity in mice was evoked by alternating current stimulation (25 mA, 500 V, 50 Hz, 0.2 s). Both, the type I isobolographic analysis and the test of parallelism of dose-response effects of the ASDs were used so as to properly classify interaction among three ASDs, administered in a fixed ratio combination of 1:1:1. RESULTS: The three-drug mixture of LCM, LTG and VPA at the fixed ratio of 1:1:1 protected the experimental mice from MES-induced seizures; however, the reported interaction was sub-additive (antagonistic; p < 0.01) with isobolography. CONCLUSION: The antagonistic pharmacodynamic interaction among LCM, LTG and VPA in the MES test in mice cannot be transferred to clinical settings and this unfavorable combination should not be recommended for patients with epilepsy.

Anticonvulsant and neurotoxic effects of a novel 1,2,4-triazole-3-thione derivative (TPF-34) and its isobolographic interaction profile with classical antiepileptic drugs in mice.

BACKGROUND: Anticonvulsant and acute toxic effects of 5-[(3-fluorophenyl)ethyl]-4-(n-hexyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPF-34)-a candidate for novel antiepileptic drug-were examined in the maximal electroshock-induced seizure (MES) model and rotarod test in mice. The interaction profile of TPF-34 with four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) was also studied in the mouse MES model. METHODS: Both ED50 and TD50 values for TPF-34 were determined at four treatment times (15, 30, 60 and 120 min after i.p. administration) in the MES model and rotarod test in adult male albino Swiss mice, respectively. The influence of TPF-34 on the protective anticonvulsant action of carbamazepine, phenobarbital, phenytoin and valproate in the mouse MES model was assessed with isobolographic analysis of interaction. Total brain antiepileptic drug concentrations were measured with fluorescence polarization immunoassay. RESULTS: TPF-34, when administered alone at four pretreatment times (15, 30, 60 and 120 min before experiments), possessed a favorable preclinical profile with the protective index (a ratio of TD50 and ED50 values) ranging from 2.89 to 3.53. Moreover, TPF-34, when combined with carbamazepine, phenobarbital, phenytoin and valproate, exerted an additive interaction in the MES model in mice. TPF-34 had no impact on total brain antiepileptic drug concentrations in mice. CONCLUSIONS: A protective index value higher than 3 allows recommending TPF-34 as a promising antiepileptic drug candidate for further preclinical testing using other experimental seizure models. The additive interaction of TPF-34 with carbamazepine, phenobarbital, phenytoin and valproate in the mouse MES model is worthy of recommendation to further clinical studies.

Health Behaviours in Scaffold Use Risk Assessment Model - SURAM.

INTRODUCTION: Problems concerning occupational safety and health are commonly found in the construction industry, including falling materials, tools or people from a height, stepping on objects, and injuries caused by hand tools. An important factor in occupational safety in the construction industry is the use of scaffolds. All scaffolds used in construction, renovation, repair (including isolating, painting and decorating) and demolition, should be erected, maintained and dismantledin accordance with safety procedures. Therefore, it is crucial to deal with the safety of scaffolds and risk assessment in the construction industry; thus, the way of undertaking the assessment and the liability of assessment seems to be essential for professionals. However, it has been found that those professionals are prone to rely heavily on their own experience and knowledge in decision-making regarding risk assessment. MATERIAL AND METHODS: The Scaffold Use Risk Assessment Model (SURAM) has been developed for assessing risk levels at various stages of the construction process in various work trades. The SURAM is the result of a research project carried out at 60 construction sites in Poland and Portugal where 504 observations have been completed including both harmful physical and chemical factors, stress level, workers' habits, as well as a hundreds ex-post reconstruction of construction accidents scenarios. RESULTS: It was found that the workers' Health Behaviour Index (HBI) seems to be a more direct predictor for development of the unsafe chain of events leading to an accident than the workload, and concentration of harmful factors at the workplace. CONCLUSIONS: The developed HBI module of SURAM seems to be beneficial for predicting high-risk construction activities, and thus preventing the occurrence of accidents, based on a set of historical accident data.

Contamination of selected recreational areas in Lublin Province, Eastern Poland, by eggs of Toxocara spp., Ancylostoma spp. and Trichuris spp.

INTRODUCTION: While using recreational areas, people take with them accompanying animals (dogs, cats). These animals are the main source and reservoir of dangerous zoonoses, including parasitoses caused by genera of nematodes, also called roundworms, Toxocara spp., Trichuris spp. and Ancylostoma spp. Attention should also be paid to the possibility of contamination of recreational areas with the eggs of intestinal parasites by wild animals (e.g. red fox). MATERIAL AND METHODS: Sand was collected on beaches and leisure terrains located in recreational areas in Zwierzyniec, Rudka reservoir on the river Wieprz, 'Echo' reservoir, accessible to tourists to the Roztocze National Park, and the 'Florianiecki' reservoir, chich is inaccessible to tourists due to its location in the depths of the National Park. Material for the research was also collected from the 'Zemborzycki reservoir in Lublin, A total of 300 sand samples were collected. The samples, approximately 500 g each, were collected into plastic bags from the superficial layer of sand, at a depth up to 3 cm. For egg detection, flotation with the Wasylikowa metod and the modified Quinn method were used. In the Quinn metod, the flotation solution is NaCl saturated solution, in the Wasylikowa method, 5% solution of NaOH is used. RESULTS: The most contaminated grounds were areas by the water 'Zemborzycki' reservoir in Lublin. The eggs of intestinal parasites were isolated from 13 out of 24 samples examined. In sand collected from the beach by the 'Echo', 'Florianiecki' and 'Rudka' water resevoirs in Zwierzyniec, no eggs of intestinal parasites were detected. CONCLUSIONS: Such a dissemination of results may indicate a connection between the degree of occurrence of geohelmint eggs and the intensity of human movement, together with accompanying animals, in places that can be used for recreation.

Tawny owl (Strix aluco) as a potential transmitter of Enterobacteriaceae epidemiologically relevant for forest service workers, nature protection service and ornithologists.

Established taxa within the Enterobacteriaceae wereisolated from cloacal swabs of Strix aluco chicks in nest boxes located at five research sites. ChromID ESBL medium (bioMerieux) was used to select a pool of Enterobacteriaceae strains producing extended-spectrum beta-lactamases. Drug sensitivity of the chosen strains was determined from the full pool of Enterobacteriaceae to 6 chemotherapeutics of different mechanisms of action. The study evaluated the sensitivity of ESBL-synthesizing isolates to substances belonging to penicillins, cephalosporins, cephamycins, clavams, carbapenems and monobactams. Analysis of the results indicated a potential role of Strix aluco in the dissemination of epidemiologically-relevant Enterobacteriaceae, and, importantly, pose health risks to forest service workers, nature protection service and ornithologists. The results can also serve as the basis for further environmental studies.

Contamination of soil with eggs of geohelminths in recreational areas in the Lublin region of Poland.

Recreational areas cover parks, bicycle paths, lawns, urban squares, sports complexes, holiday camp areas, playgrounds for children, beaches, and even spontaneously used green field open spaces. While using recreational areas, people take with them accompanying animals (dogs, cats). These animals constitute the main source and reservoir of many dangerous zoonoses, including parasitoses caused by roundworms of the genus Toxocara and Trichuris. The objective of the presented study was determination of the level of contamination of soil with parasites' developmental forms (eggs of Toxocara spp., Ascaris spp., Trichuris spp and Ancylostoma) in selected recreational areas in the Lublin Region of southeastern Poland. The material for the study was collected from beaches in recreational areas located around the Biale Lake near Wlodawa, the water reservoirs in Krasnobród and Janów Lubelski. The studies were carried out from May-October 2010 durng which time a total number of 215 samples of sand were collected. Eggs of Ascaris spp. and Trichuris spp. were detected based on the Polish Standard PN-Z-19000-4/2001. Beaches on the Biale Lake were the most contaminated. The eggs of intestinal parasites were isolated from 6 per 15 samples examined, which is 40%. In one sample, the presence of the eggs of 3 types of parasites were observed, while the eggs of Ancylostoma were not found in any of the samples. Attention should also be paid to the possibility of contamination of recreational areas with the eggs of intestinal parasites by wild animals. Recently in Poland, as well as in many other European countries, the phenomenon of synantropization of wild living animals has been observed, which most frequently concerned wild boar (Sus scrofa) and red fox (Vulpes vulpes).

[Nitazoxanide ("Alinia")--a promising antiparasitic drug]. / Nitazoksanid ("Alinia")--budzacy nadzieje lek przeciwpasozytniczy.

In present-day world intestinal parasitic infections are gaining importance as a cause of morbidity and mortality. One of the reasons behind it is the globalization and increased number of people travelling to endemic areas of parasitic diseases. Consequently, we need to treat increasing number of patients showing symptoms of such diseases. Unfortunately, the array of available and efficient antiparasitic drugs has been shrinking. Their efficacy decreases and quite often the side effects are serious. In this paper we would like to focus on a new promising "nitazoxanide" (active substance). "Nitazoxanide" proved its efficacy in the treatment of nematode-, cestode-, trematode- and protozoan infections.