Mechanism-based models in reproductive and developmental toxicology

This chapter discusses the study of the currently available models for testing developmental toxicity (embryotoxicity and teratogenicity). The main alternative models for testing developmental toxicity are described. These models are divided between validated models (whole-embryo culture test (WEC), micromass test (MM) and embryonic stem cell test (EST)) and those that are not currently validated (although have proven scientific validity) as is the case of zebrafish, frog embryo teratogenesis assay (FETAX), in silico models for predicting embryotoxicity, in vitro cellular models different from the EST method, and methods using fragments of embryos. The non-validated alternative models for testing developmental toxicity are also explained here. To date, only three in vitro methods (MM, EST and WEC) have been validated by an international agency (ECVAM) in order to be used for testing the embryotoxicity potential of chemicals, although other models such as FETAX and zebrafish have also proved their validity for this purpose. Methods based on the employment of embryos allow the specific malformation expected after exposure to the chemical to be determined, while methods based on cellular systems are more relevant in order to determine the mechanism underlying the adverse observed effect and still display a wide field for improving their prediction capability

OECD guidelines and validated methods for in vivo testing of reproductive toxicity

This chapter discusses the methods adapted by the OECD and some other protocols, including the general principles of the study, the main aspects of the procedure, the endpoints and the observations, data reporting and criteria for interpreting results, and summarizing the guidelines. OECD 414 provides general information concerning the effects of prenatal exposure on the pregnant test animal and on the developing organism. OECD 415 is designed to provide general information concerning the effects of the tested substance on male and female reproductive performance. OECD 416 test is designed to provide general information concerning the effects of a tested substance on the integrity and performance of the male and female reproductive systems, including gonadal function, the estrus cycle, mating behavior, conception, gestation, parturition, lactation and weaning, and the growth and development of the offspring. The study also provides information about the effects on the first generation (F1) including neonatal morbidity, mortality and preliminary data on prenatal and postnatal developmental toxicity. OECD 421 offers only limited means of detecting postnatal manifestations of prenatal exposure, or effects that may be induced during postnatal exposure. OECD 422 is intended for identification of possible health hazards likely to arise from repeated exposure over a relatively limited period of time. OECD 426 is designed to provide data, including dose–response characterization, on the potential functional and morphological effects on the developing nervous system of the offspring that may arise from exposure in uterus and during early life

Reproductive toxicity: in vivo testing guidelines from OECD

The guidelines for testing the reproductive toxicity in vivo developed and validated by Organisation for Economic Cooperation and Development allow for a systematic and internationally accepted testing and assessment of chemicals. Within reproductive toxicity two main categories of guidelines are usually identified: one dedicated to testing developmental toxicity, starting before the gestation period, while the other guidelines test the reproductive toxicity as a whole, therefore including male and female fertility and development. In this chapter, we summarize the guidelines on in vivo reproductive toxicity, by describing the general principles of the studies, the main aspects of the procedure, the endpoints and the observations, data reporting, and the criteria needed for the interpretation of their results

Chapter 7 - Alternative methods to animal experimentation for testing developmental toxicity

The available alternative methods for testing developmental toxicity comprise either cellular models or whole embryos of rodents, fish, or amphibian. The simplest cellular models consider the use of human or animal embryonic stem cells (embryonic or of induced pluripotency) under differentiation and one of the most widely used endpoints in these methods is the alterations in differentiated beating cardiomyocytes, although determination of other molecular markers is also extended. More complex cellular models consider the use of cocultures or 3D cultures or the so-called organoids. These models mimic the physiological environment in a much better way than the simple monolayer cultures. The use of whole embryos allows the determination of which teratogenic effects are expectable after exposure to developmental toxicants, which is one of the main disadvantages of the cellular methods. The appropriate assessment of chemical safety for development needs of a battery of alternative methods applied. Integrated Approaches to Testing and Assessment (IATA) would allow in the close future to perform safe and reliable assessment of developmental toxicity based on alternative methods

Cell Viability Effects and Antioxidant and Antimicrobial Activities of Tunisian Date Syrup (Rub El Tamer) Polyphenolic Extracts

The aqueous−acetone polyphenolic extract of the traditionally derived date syrup, known as “Rub El Tamer”, was analyzed using RP-HPLC-DAD and ESI-MS. The phenolic content of the extract was 394.53 ± 1.13 mg per 100 g of syrup with caffeoylsinapylquinic acid as the most abundant compound (72.23%). The extract exhibited strong antioxidant activities as evaluated using the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods. The extract antimicrobial potential against a range of microorganism strains showed that Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus were the most sensitive bacteria with MBC in the range of 0.5−0.05 mg/mL. Furthermore, in the presence of the syrup extract (8.18−131 μg/mL), the Human SH-SY5Y neuroblastoma and the 3T3 fibroblast cell lines showed dissimilar reduction of viability suggesting a higher cytotoxic effect against tumorigenic cells. Our results provide new insights into date syrup characterization which should stimulate further studies of this hot desert resource

Polyphenolic Extract of Barbary-Fig (Opuntia ficus-indica) Syrup: RP–HPLC–ESI–MS Analysis and Determination of Antioxidant, Antimicrobial and Cancer-Cells Cytotoxic Potentials

The traditionally derived syrup of Opuntia ficus-indica fruit is commonly used in homemade confectionery. Herein, the aqueous-acetone extract prepared from the Tunisian O. ficus-indica syrup was investigated. The qualitatively and quantitatively polyphenolic content was analysed using reversed-phase high-performance liquid chromatography–diode array detection (RP-HPLC–DAD) coupled to electrospray ionisation–mass spectrometry (ESI–MS). The extract contained 19.95 ± 2.01 mg phenolics per gram of fresh starting material with isorhamnetin 3-O-robinobioside as the major compound (22.76%). The syrup extract showed strong antioxidant potentials as assessed by both ABTS and DPPH functional methods. It exhibited effective antimicrobial activity, particularly against Staphylococcus aureus and Staphylococcus epidermidis with a minimal bactericide concentration (MBC) of 1.3 mg phenolics/ml. Furthermore, at final concentrations in the range of 41.38–186.25 μg polyphenols/ml, the extract decreased human SH-SY5Y neuroblastoma and 3T3 fibroblast in vitro cell viability in a dose- and time-dependent manner compared to non-treated control cells. The observed effects were significantly (P < 0.05) high against cancer lines. Extract concentrations higher than 106.43 μg/ml reduced cancer cells viability to 50–60% 1–3 h post-treatment. Further in vivo insight studies should emphasise and validate the herein obtained results

Cytotoxic effect against 3T3 fibroblasts cells of saffron floral bio-residues extracts

For every kilogram of saffron spice produced, about 63 kg of floral bio-residues (FB) (tepals, stamens and styles) are thrown away. Extracts of these bio-residues in water (W1), water:HCl (100:1, v/v) (W2), ethanol (E3), ethanol:HCl (100:1, v/v) (E4), dichloromethane (D5) and hexane (H6) were prepared. Their composition in flavonols and anthocyanins, and their effect on cell viability were determined. W1 was the richest in kaempferol 3-sophoroside (30.34 mg/g dry FB) and delphinidin 3,5-diglucoside (15.98 mg/g dry FB). The highest tested concentration (900 μg/ml) of W1, W2, E4, D5 and H6 did not significantly decrease the cell viability. Only E3 at that concentration caused a significant decrease of 38% in the cell viability. Therefore, all extracts studied are not cytotoxic at concentrations lower than 900 μg/ml, and W1 is proposed as the optimal for food applications due to its greater contribution of phenolic compounds

Kairos study protocol: a multidisciplinary approach to the study of school timing and its effects on health, well-being and students’ performance

Recent evidence from chronobiology, chssronomedicine and chronopsychology shows that the organisation of social time (e.g., school schedules) generally does not respect biological time. This raises concerns about the impact of the constant mismatch between students’ social and internal body clocks on their health, well-being and academic performance. The present paper describes a protocol used to investigate the problem of (de) synchronisation of biological times (chronotypes) in childhood and youth in relation to school times. It studies the effects of student chronotype vs. school schedule matches/mismatches on health behaviours (e.g., how many hours students sleep, when they sleep, eat, do physical activity, spend time outdoors in daylight) and learning (verbal expression, spatial structuring, operations) and whether alert-fatigue levels mediate this effect alignments/misalignments on learning (verbal expression, spatial structuring, operations) and their mediation by alert-fatigue levels. The novelty of our protocol lies in its multidisciplinary and mixed methodology approach to a relevant and complex issue. It draws on up-to-date knowledge from the areas of biology, medicine, psychology, pedagogy and sociology. The methods employed include a varied repertoire of techniques from hormonal analysis (cortisol and melatonin), continuous activity and light monitoring, self-registration of food intake, sleep timings, exercise and exposure to screens, alongside with systematic application of cognitive performance tests (e.g., memory, reasoning, calculation, attention) and self-reported well-being. This comprehensive and interdisciplinary protocol should support evidence-based education policy measures related to school time organisation. Appropriate and healthier school timetables will contribute to social change, healthier students and with more efficient learning. The results of studies using a similar methodology in other countries would ensure replication and comparability of results and contribute to knowledge to support policy making

Reasons for facebook usage: data from 46 countries

info:eu-repo/semantics/publishedVersio

Predictors of Enhancing Human Physical Attractiveness: Data from 93 Countries

People across the world and throughout history have gone to great lengths to enhance their physical appearance. Evolutionary psychologists and ethologists have largely attempted to explain this phenomenon via mating preferences and strategies. Here, we test one of the most popular evolutionary hypotheses for beauty-enhancing behaviors, drawn from mating market and parasite stress perspectives, in a large cross-cultural sample. We also test hypotheses drawn from other influential and non-mutually exclusive theoretical frameworks, from biosocial role theory to a cultural media perspective. Survey data from 93,158 human participants across 93 countries provide evidence that behaviors such as applying makeup or using other cosmetics, hair grooming, clothing style, caring for body hygiene, and exercising or following a specific diet for the specific purpose of improving ones physical attractiveness, are universal. Indeed, 99% of participants reported spending \u3e10 min a day performing beauty-enhancing behaviors. The results largely support evolutionary hypotheses: more time was spent enhancing beauty by women (almost 4 h a day, on average) than by men (3.6 h a day), by the youngest participants (and contrary to predictions, also the oldest), by those with a relatively more severe history of infectious diseases, and by participants currently dating compared to those in established relationships. The strongest predictor of attractiveness-enhancing behaviors was social media usage. Other predictors, in order of effect size, included adhering to traditional gender roles, residing in countries with less gender equality, considering oneself as highly attractive or, conversely, highly unattractive, TV watching time, higher socioeconomic status, right-wing political beliefs, a lower level of education, and personal individualistic attitudes. This study provides novel insight into universal beauty-enhancing behaviors by unifying evolutionary theory with several other complementary perspectives