Paradigm lost, paradigm found: the re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted.     

Geologic emissions of methane to the atmosphere

The atmospheric methane budget is commonly defined assuming that major sources derive from the biosphere (wetlands, rice paddies, animals, termites) and that fossil, radiocarbon-free CH4 emission is due to and mediated by anthropogenic activity (natural gas production and distribution, and coal mining). However, the amount of radiocarbon-free CH4 in the atmosphere, estimated at approximately 20% of atmospheric CH4, is higher than the estimates from statistical data of CH4 emission from fossil fuel related anthropogenic sources. This work documents that significant amounts of "old" methane, produced within the Earth crust, can be released naturally into the atmosphere through gas permeable faults and fractured rocks. Major geologic emissions of methane are related to hydrocarbon production in sedimentary basins (biogenic and thermogenic methane) and, subordinately, to inorganic reactions (Fischer-Tropsch type) in geothermal systems. Geologic CH4 emissions include diffuse fluxes over wide areas, or microseepage, on the order of 10(0)-10(2) mg m(-2) day(-1), and localised flows and gas vents, on the order of 10(2) t y(-1), both on land and on the seafloor. Mud volcanoes producing flows of up to 10(3) t y(-1) represent the largest visible expression of geologic methane emission. Several studies have indicated that methanotrophic consumption in soil may be insufficient to consume all leaking geologic CH4 and positive fluxes into the atmosphere can take place in dry or seasonally cold environments. Unsaturated soils have generally been considered a major sink for atmospheric methane, and never a continuous, intermittent, or localised source to the atmosphere. Although geologic CH4 sources need to be quantified more accurately, a preliminary global estimate indicates that there are likely more than enough sources to provide the amount of methane required to account for the suspected missing source of fossil CH4.     

Performance of a narrow buffer strip in abating agricultural pollutants in the shallow subsurface water flux

The performance of a narrow buffer strip in abating dissolved P, electrical conductivity and herbicides (terbuthylazine, alachlor, nicosulfuron, pendimethalin, linuron) in subsurface water coming from cropland was tested in an experiment carried out on the low plains of the Veneto Region (NE Italy). The experiment lasted from December 1997 to June 1999, monitoring subsurface water quality entering and exiting a buffer composed of a grass strip (5 m wide) and 1 m wide row of trees. Dissolved phosphorus concentrations were reduced by almost 100% passing through the buffer and in most cases exiting water satisfied the limit for avoiding eutrophication. A positive effect was also detected on ECW (reduced by 20%), while pH was not significantly altered. Herbicide concentration abatement varied between 60 and 90%, depending on the chemical and the time elapsed since application.     

Fetal echocardiography using transvaginal and transabdominal probes during the first period of pregnancy: A comparative study

The authors compare the diagnostic possibilities of fetal transabdominal echocardiography versus transvaginal echocardiography. A larger diagnostic capacity is verified in different gestation ages with transvaginal probe between the 11th and 14th week of gestation. The results are emphasized by colour Doppler.     

Sister chromatid exchanges in first-trimester chorionic villi after in vivo and in vitro exposure to diagnostic ultrasound

A study was done to evaluate the effects of diagnostic ultrasound on sister chromatid exchange (SCE) in first-trimester chorionic villi under controlled technical conditions. Chromosome analysis was performed by the direct method using spontaneous mitoses from the cytotrophoblast layer, and SCE visualization was accomplished by a 72 h treatment with 5-bromodeoxyuridine (BrdU) at a concentration of 10μg/ml. The slides were stained with ac ridine orange. Immediately before first-trimester chorionic villus sampling, a group of ten pregnant women was exposed to diagnostic ultrasound for 20min (in vivo exposure). This group of patients was compared with a control group who were not exposed. A mean value of SCE/cell frequency of 4·2 ± 0·2 was found in the exposed pregnancies, while a value of 3·7 ± 0·2 was observed in the control group. After in vitro exposure of chorionic villi obtained from elective abortions, the frequency of SCE/cell did not differ significantly among samples with different exposures (1,2, and 3 h) and controls. The positive control (mitomycin C) yielded a significant increase in SCE frequency.     

Prenatal diagnosis of congenital human cytomegalovirus infection

Fifteen fetuses at risk of congenital human cytomegalovirus (HCMV) infection underwent prenatal diagnosis at 16–30 weeks' gestation by a combination of amniocentesis and fetal blood sampling. HCMV was isolated from the amniotic fluid in six patients, but HCMV-specific IgM was detected in only three of them. Two of the nine neonates, who were delivered following a negative prenatal diagnosis, had congenital HCMV infection diagnosed by virus isolation in the urine. The interval from infection to prenatal testing was 3 and 4 weeks in the two false-negative cases and ⩾ 7 weeks in the true-positive cases. Although timely testing for HCMV infection allows the option of termination of pregnancy, it may be flawed by false-negative results.     

Amiodarone treatment in pregnancy for dilatative cardiomyopathy with ventricular malignant extrasystole and normal maternal and neonatal outcome

Amiodarone treatment in pregnancy might be difficult to handle because of the long half-life of the drug (14–28 days up to 2 months) and because it reduces maternal and neonatal thyroid activity. Although short-term use in pregnancy has been described in cases of fetal supraventricular tachycardia, there are few reports on the chronic use of the drug. In this paper we describe our experience with amiodarone treatment in two pregnant sisters with familial dilatative cardiomyopathy and ventricular malignant extrasystole. Prolonged administration of amiodarone (400–200 mg/die) since the beginning of pregnancy did not have any adverse effects; maternal and neonatal thyroid function was normal, as was the neurological and motor development of the neonates.     

Early prenatal sonographic diagnosis of neuropathic arthrogryposis multiplex congenita with osseous heterotopia

A prenatal diagnosis of arthrogryposis multiplex congenita (AMC) has been carried out on a 19-week-old fetus by means of echography. The ultrasonographic characteristics were unnatural position of the four limbs associated with articular anomalies together with absence of active fetal movements. A therapeutic interruption of pregnancy was performed and the diagnosis was confirmed. At autopsy, architectural disorder of the motor neurons of the anterior medullary horn revealed a neuropathic pathogenesis of the arthrogryposis. Moreover, at the lumbar level the spinal cord was progressively replaced by heterotopic bony tissue which caused a more severe deformity of the lower limbs compared with the upper. The aspects of anatomo-pathological, genetic, and differential diagnosis are discussed showing the precocity of the prenatal diagnosis and the peculiarity of the aetiology of our case.     

Parent-absent signalling of need and its consequences for sibling competition in the barn swallow

In species with parental care, competition among siblings for access to limited parental resources is common. Sibling competition can be mediated by begging behaviour, a suite of different visual and acoustic displays by which offspring solicit parental care. These are mostly addressed to the parents upon food provisioning, but can also be performed in the absence of the attending parents. This so-called parent-absent begging (PAB) may function as an intrabrood communication signal and potentially affect intrabrood competition dynamics for access to food. We investigated the role of PAB in moulding sibling interactions and its effect on food intake among altricial barn swallow (Hirundo rustica) nestlings, both under normal and experimentally reduced food intake. Frequency of PAB increased after food deprivation. Nestlings that had performed PAB increased their begging intensity upon the subsequent parental feeding visit, while siblings reduced their own begging level, but only when they had not been food-deprived. As a consequence, nestlings which had performed PAB before parental arrival had larger chances of receiving food. However, nestlings did not benefit from displaying PAB when competing with food-deprived siblings. Our findings show that PAB reliably reflects need of food, indicating that a nestling will vigorously compete for the subsequent food item. By eavesdropping siblings' PAB displays, nestlings may optimally balance the costs of scrambling competition, the direct fitness gains of being fed and the indirect fitness costs of subtracting food to needy kin. However, large asymmetries in satiation between competitors may lead individual offspring to monopolize parental resources, irrespective of PAB displays.