Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model.

BACKGROUND: Titanium dioxide (TiO2) is broadly used in common consumer goods, including as a food additive (E171 in Europe) for colouring and opacifying properties. The E171 additive contains TiO2 nanoparticles (NPs), part of them being absorbed in the intestine and accumulated in several systemic organs. Exposure to TiO2-NPs in rodents during pregnancy resulted in alteration of placental functions and a materno-foetal transfer of NPs, both with toxic effects on the foetus. However, no human data are available for pregnant women exposed to food-grade TiO2-NPs and their potential transfer to the foetus. In this study, human placentae collected at term from normal pregnancies and meconium (the first stool of newborns) from unpaired mothers/children were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and scanning transmission electron microscopy (STEM) coupled to energy-dispersive X-ray (EDX) spectroscopy for their titanium (Ti) contents and for analysis of TiO2 particle deposition, respectively. Using an ex vivo placenta perfusion model, we also assessed the transplacental passage of food-grade TiO2 particles. RESULTS: By ICP-MS analysis, we evidenced the presence of Ti in all placentae (basal level ranging from 0.01 to 0.48 mg/kg of tissue) and in 50% of the meconium samples (0.02-1.50 mg/kg), suggesting a materno-foetal passage of Ti. STEM-EDX observation of the placental tissues confirmed the presence of TiO2-NPs in addition to iron (Fe), tin (Sn), aluminium (Al) and silicon (Si) as mixed or isolated particle deposits. TiO2 particles, as well as Si, Al, Fe and zinc (Zn) particles were also recovered in the meconium. In placenta perfusion experiments, confocal imaging and SEM-EDX analysis of foetal exudate confirmed a low transfer of food-grade TiO2 particles to the foetal side, which was barely quantifiable by ICP-MS. Diameter measurements showed that 70 to 100% of the TiO2 particles recovered in the foetal exudate were nanosized. CONCLUSIONS: Altogether, these results show a materno-foetal transfer of TiO2 particles during pregnancy, with food-grade TiO2 as a potential source for foetal exposure to NPs. These data emphasize the need for risk assessment of chronic exposure to TiO2-NPs during pregnancy.

The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota.

BACKGROUND: Alterations of intestinal microbiota and hypersensitivity to colonic distension are two features of the irritable bowel syndrome (IBS). However, the role of intestinal microbiota in visceral hypersensitivity of IBS patients is far to be established. The aim of our study was to determine whether the intestinal microbiota is involved in the visceral hypersensitivity in IBS. METHODS: The painful response to colorectal distension and colonic mucosal parameters were assessed in gnotobiotic rats. Germfree (GF) rats were inoculated with the fecal microbiota from IBS patients characterized by hypersensitivity to colorectal distension (IBS HMA rats) or from non-hypersensitive healthy volunteers (Healthy HMA rats). Conventional rats were studied as normosensitivity control. Fecal microbial analyses were carried out in human and HMA rats fecal samples using cultural and molecular approaches. KEY RESULTS: The microbial dysbiosis of the IBS gut microbiota (more sulfate-reducing bacteria and Enterobacteriaceae and less bifidobacteria) could be maintained in gnotobiotic rats. The number of abdominal contractions in response to colorectal distensions was significantly higher in IBS HMA rats than in healthy HMA rats. No difference was observed between healthy HMA and conventional rats. Colorectal compliance, epithelial paracellular permeability, and density of colonic mucosal mast cells were similar in the three groups of rats. CONCLUSIONS & INFERENCES: We herein showed that sensitivity to colonic distension of IBS patients can be transferred to rats by the fecal microbiota. Mucosal alterations associated with microbiota transfer are not involved in this hypersensitivity. The altered IBS microbiota may have important role in the hypersensitivity characterizing IBS patients through specific bacterial metabolites.

Efficacy of dog-appeasing pheromone in reducing behaviours associated with fear of unfamiliar people and new surroundings in newly adopted puppies.

This study was designed to determine the potential value of dog-appeasing pheromone (DAP) in reducing behaviours associated with fear of unfamiliar people and new surroundings in puppies newly adopted from a pet shop. The study was triple-blinded, randomised and placebo-controlled. It used 66 puppies (32 fitted with a DAP collar and 34 control) and the adoptive owners were contacted by phone three days and 15 days after they had adopted the puppy to question them about its reactions to specific situations eliciting fear. Fifteen days after the treatments significantly fewer of the puppies with the DAP collars showed signs of fear when facing unfamiliar people at home and/or during outings. This difference was irrespective of breed size.

Efficacy of dog-appeasing pheromone in reducing stress associated with social isolation in newly adopted puppies.

This study was designed to determine the potential value of dog-appeasing pheromone (dap) in reducing stress in puppies newly adopted from a pet shop. The trial was triple-blinded and placebo-controlled. After their arrival at the pet shop, 32 puppies were fitted with a dap collar and 34 were fitted with a control collar, according to a randomisation protocol. Adopting owners were contacted by telephone, three and 15 days after they had adopted a puppy, to obtain information about the puppy's integration into the family, and particularly about any signs of distress shown by the puppy when it was socially isolated. All the isolated puppies from the control group vocalised during the first night. Signs of distress, particularly vocalisation, were significantly lower in the dap group on day 3 and throughout the rest of the study, and vocalisation during the night ceased significantly sooner in this group. These differences were observed in puppies of small, medium and large breeds. The dap collars had no effect on the incidence of house soiling.

Comparison of the efficacy of a synthetic dog-appeasing pheromone with clomipramine for the treatment of separation-related disorders in dogs.

Sixty-seven dogs that showed signs of distress when separated from their owners (destructiveness, excessive vocalisation and house soiling) and hyperattachment were used in a randomised, blind trial to assess the potential value of a dog-appeasing pheromone in reducing the unacceptable behaviours. For ethical reasons, there was no placebo group and the effects of the pheromone were compared with the effects of clomipramine which is regularly used to treat this type of problem. The undesirable behaviours decreased in both groups, but the overall assessment by the owners indicated that there was no significant difference between the two treatments, although there were fewer undesirable events in the dogs treated with the pheromone, and the administration of the pheromone appeared to be more convenient.

Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of action.

The involvement of neurokinin receptors in visceral nociception is well documented. However, the role and localization of NK3 receptors is not clearly established. This study was designed to determine whether NK3 receptor antagonists crossing (talnetant) or not (SB-235375) the blood-brain barrier reduce the nociceptive response to colo-rectal distension (CRD) and whether NK3 antagonism reduces inflammation- or stress-induced hypersensitivity to rectal distension. Isobaric CRD and isovolumic rectal distensions were performed in rats equipped with intramuscular electrodes to record abdominal muscle contractions. In controls, CRD induced a pressure-related (15-60 mmHg) increase in the number of abdominal contractions. Both talnetant and SB-235375 [50 mg x kg-1, per oral (p.o.)], which had no effect on colo-rectal tone, reduced the number of contractions associated with CRDs from 30 to 60 mmHg. Three days after rectal instillation of TNBS, abdominal contractions were increased for rectal distension volume of 0.4 mL. This effect was not modified by talnetant (30 mg x kg-1, p.o.). Partial restraint stress increased abdominal contractions at all distension volumes (0-1.2 mL). Talnetant (10 mg kg-1, p.o.) abolished the increase observed for 0.8 and 1.2 mL. These results indicate that peripheral NK3 receptor antagonism reduced nociception associated with CRD and hypersensitivity induced by stress but not inflammation.