Environmental correlates of growth patterns in Neolithic Liguria (northwestern Italy).

OBJECTIVE: This study evaluates patterns of human growth in the Neolithic to make inferences about environmental correlates of developmental disturbances. MATERIALS: 33 children/adolescents from the Neolithic of Liguria (Italy), 29 of which date between 4,800-4,400 cal BCE. METHODS: Neolithic patterns of growth are compared with a modern sample (the Denver Growth Study; DGS). Dental development was used to determine age at death. Proxies for postcranial maturation are femoral length and proportion of mean adult femoral length attained. RESULTS: Ligurian children show growth faltering compared to DGS, especially between 4 and 9 years of age. Between 1 and 2 years, and in later childhood and adolescence, values are more similar or higher than DGS, when using the proportion of adult femoral length attained. CONCLUSIONS: The pattern of growth in Ligurian Neolithic children may reflect a deprived and highly-infectious environment: three individuals show skeletal lesions consistent with tuberculosis. The relatively faster growth in infancy may result from the buffering provided by maternal milk. Older children and adolescents may exhibit catch-up growth. SIGNIFICANCE: This study contributes to our understanding of Neolithic selective pressures and possible biocultural adaptive strategies. LIMITATIONS: The cross-sectional nature of the data and the small sample size make it unclear whether the observed pattern is representative of the growth patterns in the living population. The possibility that adults are stunted undermines the interpretation of optimal growth in the first years. SUGGESTIONS FOR FURTHER RESEARCH: Refine age estimates, increase sample size through the study of other bone elements.

Detection of Naegleria spp. and Naegleria fowleri: a comparison of flagellation tests, ELISA and PCR.

To detect Naegleria spp, in particular Naegleria fowleri, the causative agent of human primary amoebic meningoencephalitis, a flagellation test (FT) is routinely used followed by a specific ELISA. A positive FT indicates the presence of Naegleria spp although some false negatives are likely to occur since parameters for enflagellation vary greatly. As negative FTs are not routinely screened any further for the presence of N. fowleri, this could result in an underestimation of the presence of this pathogen. Therefore, amoebae were further analysed using ELISA and standard PCR not only after a positive but also after a negative FT. In this study 39 cultures containing amoebae were tested with FT, ELISA and the two PCR assays with 11 positive for FT. These were submitted to ELISA and four confirmed as N. fowleri. PCR with the common primer-set on these 11 positive FTs revealed all as Naegleria spp. The specific PCR used on these cultures detected four positive for N. fowleri, corresponding totally with the ELISA results. The 28 negative flagellation tests were also submitted to ELISA and PCR. Of these, 11 were identified as Naegleria spp with common PCR and six as N. fowleri as well as with ELISA and the specific PCR. When the detection of Naegleria spp is based on intermediary processes, such as flagellation tests, false negatives are likely to occur leading to severe underestimations. This study has shown that amoebae taken from negative FTs can be identified as Naegleria spp and N. fowleri when using PCR and ELISA. The application of at least one of the specific N. fowleri tests is recommended for routine screening. The heterogeneous distribution of the false negative results between the different power plants suggested the presence of different genotypes.

Intravascular and intracellular hepatic relaxivities of superparamagnetic particles: an isolated and perfused organ pharmacokinetics study.

The relative contributions of intravascular and intracellular compartments to the proton transverse relaxation of the isolated and excised rat liver were determined during the phagocytosis of superparamagnetic particles. The evolution of the proton transverse magnetization of the organ perfused with increasing doses of starch-coated magnetic microspheres was followed up using a Carr-Purcell-Meiboom-Gill sequence with various echo times. From the multiexponential fit of the echo train, the amplitudes and the relaxation rates R2 of the liver tissue were obtained. The results clearly indicate that shortly after contrast medium administration, an internalization takes place which can be followed by the rapid and biphasic evolution of the transverse relaxation rate of the water protons. A very fast decaying component looking like an initial loss of the magnetization is observed together with an increase of the relaxation rate of the remaining water tissue. This regime is strongly dependent on both the echo time and the iron concentration, a behavior characteristic of the agglomeration of magnetic particles. The examination of the liver tissues by electron microscopy shows that this clustering arises in cytoplasmic vacuoles.

A multinuclear MR study of Gd-EOB-DTPA: comprehensive preclinical characterization of an organ specific MRI contrast agent.

The characterization of the hepatobiliary contrast agent Gd-EOB-DTPA (gadolinium 3, 6, 9-triaza-3, 6, 9-tris(carboxymethyl)-4-(4-ethoxybenzyl)-undecandicarboxylic acid) in various media (water solution, protein containing solution, phosphorylated metabolites solution, and excised and perfused liver) was performed using different NMR approaches: water 1H nuclear magnetic relaxation dispersion profiles, 2H NMR longitudinal and transverse relaxation rates of labeled complex, water 17O transverse relaxation rates and chemical shifts, 31P relaxation rates and peak area of phosphorylated metabolites. The higher proton relaxivity of Gd-EOB-DTPA in water compared with Gd-DTPA is related to a shorter distance (r) between the water proton and the gadolinium ion and to a longer rotational correlation time (tauR) of the hydrated complex. Although the thermodynamic stability of Gd-EOB-DTPA is identical to the one of Gd-DTPA, its kinetic stability in solutions containing phosphorylated metabolites (ATP, phosphocreatine, and inorganic phosphate) as measured by 31P relaxation rates analysis is higher than for the parent compound. Gd-EOB-DTPA binds noncovalently to serum proteins. Its interaction with human serum albumin is characterized by a dissociation constant of 1-4.1 mM as calculated from proton and deuterium relaxation rates and equilibrium dialysis. This noncovalent interaction involves the subdomain IIA of human serum albumin. 31P spectroscopy of the excised and perfused rat livers was used to monitor the uptake of Gd-EOB-DTPA by the hepatocytes where it enhances the nuclear relaxation of the intracellular metabolites without impairing the adenosine triphosphate metabolism of the cells.

Multinuclear MR characterization of a new hepatobiliary contrast agent. Preliminary results.

PURPOSE: The aim of this work was to characterize the hepatobiliary contrast agent Gd-EOB-DTPA in various media: water solution, protein solution, phosphorylated metabolite solution, and excised and perfused liver tissue. MATERIAL AND METHODS: Different NMR techniques were used: analyses of H-1 NMRD profiles, H-2 NMR relaxation rates, O-17 relaxation rates and chemical shifts, and P-31 relaxation rates and peak area. RESULTS: The higher proton relaxivity of Gd-EOB-DTPA in water as compared to that of Gd-DTPA is due to a smaller distance r and to a longer tau R. The kinetic stability of the former compound in ATP solution is higher and it forms noncovalent bonds with human serum albumin. Internalization of the contrast agent by the hepatocytes does not impair the ATP metabolism of the cells but induces relaxation effects on the intracellular metabolites of the liver. CONCLUSION: Multinuclear MR studies allow the extensive characterization of MR contrast agents in in-vitro and ex-vivo model systems.