Timescales of developmental toxicity impacting on research and needs for intervention

Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome. The desire to obtain a high degree of certainty and verification of the evidence used for decision‐making must be weighed against the costs and necessary duration of research, as well as the long‐term costs to human health because of delayed protection of vulnerable early‐life stages of human development and, possibly, future generations. Although two‐generation toxicology tests may be useful for initial test purposes, other rapidly emerging tools need to be seriously considered from computational chemistry and metabolomics to CLARITY‐BPA‐type designs, big data and population record linkage approaches that will allow efficient generation of new insight; epigenetic mechanisms may necessitate a set of additional regulatory tests to reveal such effects. As reflected by the Prenatal Programming and Toxicity (PPTOX) VI conference, the current scientific understanding and the timescales involved require an intensified approach to protect against preventable adverse health effects that can harm the next generation and generations to come. While further research is needed, the main emphasis should be on research translation and timely public health intervention to avoid serious, irreversible and perhaps transgenerational harm.     

The relationship of structure,thermal and water vapor permeability barrier properties of poly(butylene succinate)/organomodified beidellite clay bionanocomposites prepared by in situ polycondensation

The exploitation of beidellite clay (BDT), used as a nanofiller in the preparation of poly(butylene succinate) (PBS)/organoclay biodegradable nanocomposites, was investigated. A series of bionanocomposites with various loadings of the organoclay (3CTA-BDT) were prepared by in situ polycondensation reaction between succinic anhydride (SuAh) and 1,4-butanediol (1,4-BD) at atmospheric pressure in refluxing decalin with azeotropic removal of water, and the reaction was catalyzed by non-toxic bismuth chloride (BiCl₃). X-ray diffraction (XRD) and scanning electron microscopy (SEM) results showed that 3CTA-BDT was likely exfoliated and well dispersed in PBS matrix. Thermal properties (TGA, DSC and thermal conductivity), contact angle measurements and water vapor sorption behavior of the corresponding nanocomposites were also discussed. Compared to pure PBS, a significant reduction of the diffusion coefficient and the water vapor permeability (WVP) by 44 and 37%, respectively, was observed by adding only 5 wt% of 3CTA-BDT. These results could make these bionanocomposites suitable materials for food packaging application.

The exploitation of beidellite clay (BDT), used as a nanofiller in the preparation of poly(butylene succinate) (PBS)/organoclay biodegradable nanocomposites, was investigated. Their thermal and water vapor barrier properties were also studied.     

Thymoquinone protects rat liver after partial hepatectomy under ischaemia/reperfusion through oxidative stress and endoplasmic reticulum stress prevention

Ischaemia reperfusion (I/R) is associated with liver injury and impaired regeneration during partial hepatectomy (PH). The aim of this study was to investigate the effect of thymoquinone (TQ), the active compound of essential oil obtained from Nigella sativa seeds, on rat liver after PH. Male Wistar rats were divided equally into four groups (n = 6) receiving an oral administration of either vehicle solution (sham and PH groups) or TQ at 30 mg/kg (TQ and TQ + PH groups) for 10 consecutive days. Then, rats underwent PH (70%) with 60 minutes of ischaemia followed by 24 hours of reperfusion (PH and TQ + PH groups). Alanine aminotransferase (ALT) activity and histopathological damage were determined. Also, antioxidant parameters, liver regeneration index, hepatic adenosine triphosphate (ATP) content, endoplasmic reticulum (ER) stress and apoptosis were assessed. In response to PH under I/R, liver damage was significantly alleviated by TQ treatment as evidenced by the decrease in ALT activity (P < .01) and histological findings (P < .001). In parallel, TQ preconditioning increased hepatic antioxidant capacities. Moreover, TQ improved mitochondrial function (ATP, P < .05), attenuated ER stress parameters and repressed the expression of apoptotic effectors. Taken together, our results suggest that TQ preconditioning could be an effective strategy to reduce liver injury after PH under I/R. The protective effects were mediated by the increase of antioxidant capacities and the decrease of ER stress and apoptosis.     

Is elevated plasma lactate a useful marker in the evaluation of pure carbon monoxide poisoning?

Objective To examine whether CO poisoning induces a significant increase in plasma lactate concentration.Design and setting Prospective observational clinical study in the emergency department and intensive care unit in a university-affiliated teaching hospital.Patients 146 pure CO poisonings resulting from dysfunction of gas cookers or water heaters.Measurements and results Patients were classified into four neurological impairment groups: 37% were severely, 8% moderately, and 45% mildly intoxicated, while 1% were asymptomatic. We found only very mild increases in plasma lactate concentration (median 2.30 mmol/l) which, however, was significantly correlated with the severity of neurological impairment and blood CO concentration (1.41 mmol/l, Spearman's test r=0.3).Conclusions Plasma lactate is mildly elevated in pure CO-exposed patients. This mild increase and the extensive overlap between the groups of neurological impairment severity do not suggest the usefulness of systematic plasma lactate measurement in pure CO poisoning.     

Serum lactate dehydrogenase and its isoenzymes in nasopharyngeal carcinoma in Tunisia

Our prospective study interested 41 patients, from 13 to 70 years old, and present a nasopharyngeal carcinoma confirmed histologically, during the period going from September 1999 to March 2000, and 45 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure serum LDH and its isoenzymes. Two groups of patients were selected after a period varying from 12 to 37 months with a mean of 29 months: 29 with favourable evolution, 12 with non favourable evolution. The mean serum total LDH and its isoenzymes values were significantly higher in patients than those in controls with values of variable p of 0.001 to 0.05. A significant correlation was found between ganglionnary extension and serum values of total LDH, LDH3 and LDH5. No significant difference were observed between the means serum total LDH before treatment and the clinical evolution of patients. Diagnostic contribution of total LDH is limited, by its ubiquitary character, but could constitute for LDH3 a good marker of the disease progression.     

Induction of infertility in adult male bonnet monkeys by immunization with phage-expressed peptides of the extracellular domain of FSH receptor

Active immunization of proven fertile adult male bonnet monkeys (Macaca radiata) with phage-expressed follicle-stimulating hormone receptor (FSHR)-specific peptides from the extracellular domain resulted in a progressive drop in sperm count with all animals becoming azoospermic by day 100. However, serum testosterone concentrations were unaltered during the entire course of study and animals exhibited normal mating behaviour. Breeding studies with proven fertile female monkeys revealed that all the immunized males were infertile. Following interruption of immunization on day 225, sperm counts returned to normal with restoration of fertility. These results indicate that infertility can be induced in adult male monkeys by interfering with the action of FSH using specific peptides of the extracellular domain of FSHR as antigens, without the risk of producing cross-reacting antibodies to the other glycoprotein hormones.     

Delayed transient loss of consciousness in acute carbon monoxide intoxication

In acute carbon monoxide intoxication the presence of altered consciousness, ranging from transient loss of consciousness to coma, represents a poor prognostic factor and modifies the approach to therapy. Transient loss of consciousness is, as a rule, contemporaneous to the exposure, generally occurring at the scene of the intoxication. We report an unusual case of delayed transient loss of consciousness, occurring in the absence of any other evident aetiology, in one member of an orchestra composed of 110 members after a mass carbon monoxide poisoning.