Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

The pesticide paraquat (PQ) was found to be a suitable xenobiotic to model Parkinson’s disease. The reactive oxygen species (ROS) production was suggested to be the main cause of PQ toxicity but very few evidences were found for its generation in the brain in vivo after ip administration. We compared the effects of PQ-induced ROS generation between the brain structures and the peripheral tissues using two different hydroxyl radical generation markers. Repeated but not single ip PQ administration increased the levels of ROS in the striatal homogenates but, when measured in the extracellular microdialysis filtrate, no change was observed. The increased dopamine release was detected in the striatum after the fourth PQ administration and its basal levels were decreased. A single treatment with the pesticide did not influence ROS production in the lungs or kidneys but repeated intoxication decreased its levels. These results suggest that repeated, systemic administration of a low dose of PQ triggers intracellular ROS formation in the brain and can cause slowly progressing degenerative processes, without the toxic effects in the peripheral tissues.     

Urinary yttrium excretion and effects of yttrium chloride on renal function in rats

Evaluation of yttrium exposure in biological samples has not been fully examined. To evaluate yttrium nephrotoxicity, yttrium chloride was orally administered to male Wistar rats and the urine volume (UV) and N-acetyl-beta-D-glucosaminidase (NAG) and creatinine excretion (Crt) were measured in 24-h urine samples. The urinary yttrium concentration and excretion rate were determined by inductively coupled plasma-argon emission spectrometry (ICP-AES). Large significant decreases of UV (>30%) and Crt (>10%) were observed at yttrium doses of 58.3-116.7 mg per rat, but no significant NAG changes was observed. This response pattern shows that a high yttrium dosage alters glomerular function rather than the proximal convoluted tubules. A urinary yttrium excretion rate of 0.216% and good dose-dependent urinary excretion (r=0.77) were confirmed. These results suggest that urinary yttrium is a suitable indicator of occupational and environmental exposure to this element, an increasingly important health issue because recent technological advances present significant potential risks of exposure to rare earth elements. We propose that the ICP-AES analytical method and animal experimental model described in this study will be a valuable tool for future research on the toxicology of rare earth elements.     

Urinary and serum titanium: assessment as an indicator of exposure to ammonium citratoperoxotitanate (IV) and its influence on renal function

Ammonium citratoperoxotitanate IV (TAS-FINE) is a water-soluble titanium complex used to synthesize a photocatalytic titanium(IV) oxide film. This study was aimed to investigate the LD50, dose-response, time-course response, and renal toxicity of TAS-FINE using an animal model. Serum titanium (S-Ti) and its 24-h urinary excretion (U-Ti) were determined by inductively coupled plasma-argon emission spectrometry (ICPAES) after a single oral TAS-FINE administration to male Wistar rats. The LD50 of TAS-FINE was 7.97 g/kg body weight in 24 h, and its half-life was 3.78+/-1.28 d for S-Ti and 2.19+/-0.09 d for U-Ti. Although TAS-FINE was not easily absorbed in the gastrointestinal tract, it was distributed into the bloodstream in a dose-dependent manner. Within 24 h, 0.189% of administrated Ti was excreted via urine. It was speculated that TAS-FINE formed conjugates with serum constituents that resulted in nephrotoxicity resulting from an allergic reaction. The observed indices in this study were revealed to be good indicators for TAS-FINE exposure. The analytical method and animal model described in this study will help to further elucidate details about human exposure to TAS-FINE, which in recent times has become an occupational and environmental toxicant of concern.     

A CTX family cell adhesion molecule, JAM4, is expressed in stem cell and progenitor cell populations of both male germ cell and hematopoietic cell lineages

Stem cells are maintained in an undifferentiated state by interacting with a microenvironment known as the "niche," which is comprised of various secreted and membrane proteins. Our goal was to identify niche molecules participating in stem cell-stem cell and/or stem cell-supporting cell interactions. Here, we isolated genes encoding secreted and membrane proteins from purified male germ stem cells using a signal sequence trap approach. Among the genes identified, we focused on the junctional adhesion molecule 4 (JAM4), an immunoglobulin type cell adhesion molecule. JAM4 protein was actually localized to the plasma membrane in male germ cells. JAM4 expression was downregulated as cells differentiated in both germ cell and hematopoietic cell lineages. To analyze function in vivo, we generated JAM4-deficient mice. Histological analysis of testes from homozygous nulls did not show obvious abnormalities, nor did liver and kidney tissues, both of which strongly express JAM4. The numbers of hematopoietic stem cells in bone marrow were indistinguishable between wild-type and mutant mice, as was male germ cell development. These results suggest that JAM4 is expressed in stem cells and progenitor cells but that other cell adhesion molecules may substitute for JAM4 function in JAM4-deficient mice both in male germ cell and hematopoietic lineages.     

Development and maturation of thymic dendritic cells during human ontogeny

Thymic dendritic cells (TDC) are dendritic cells situated mainly in the cortico-medullary zone and in the medullary region of the thymus. However, the phenotype of TDC during ontogeny is poorly documented. The aim of this study has been to investigate the development and maturation of TDC during human ontogeny. Immunohistochemical analyses and immunoelectron-microscopic investigation of 21 human thymus specimens have been performed to detect the subtypes of TDC by using various DC-related and DC-development-related markers. TDC express a Langerhans-cell-like phenotype during human ontogeny. Cells expressing thymic stromal lymphopoietin receptor have been observed in Hassal’s corpuscles of the thymus. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is also expressed in thymic epithelial cells (TEC) localized in Hassal’s corpuscles. During human ontogeny, GM-CSF is produced by TEC of Hassal’s corpuscles and might play a key role in the differentiation of TDC having Langerhans-cell-like phenotypes.     

Foraging Patch Selection and Departure by Non-Omniscient Foragers: A Field Example in White-Fronted Geese

Animals often face great uncertainty as to the quality of foraging patches. There have been a number of theoretical studies investigating how non‐omniscient predators, i.e. predators that are unable to assess foraging patch quality prior to patch exploitation, should forage in a heterogeneous environment, but empirical studies, especially in the field, are scarce. This paper describes the way in which white‐fronted geese Anser albifrons forage on harvest remains of rice, focusing on the processes of patch selection and departure. Not only in autumn, but also in spring when rice depletion has progressed, patch rice density showed no positive effect on patch selection by geese, indicating the incapability of geese to select the most profitable patch. Instead, the geese tended to select patches with a large proportion of rice fields that were near the roost and a previously visited patch and bordered by a small number of windbreaks only. The rice consumption volume by geese increased with increasing initial rice density, while giving‐up density was independent of initial rice density and was positively correlated to the mean rice density of the habitat. This suggests that the geese could compensate their lack of information on patch quality at the moment of patch selection by leaving less profitable patches earlier. We discuss the necessity of predictive models based on random patch selection and an appropriate departure rule to explain the distribution of individuals of species with limited information on patch quality.     

Biophysics of sphingolipids I. Membrane properties of sphingosine, ceramides and other simple sphingolipids

Some of the simplest sphingolipids, namely sphingosine, ceramide, some closely related molecules (eicosasphingosine, phytosphingosine), and their phosphorylated compounds (sphingosine-1-phosphate, ceramide-1-phosphate), are potent metabolic regulators. Each of these lipids modifies in marked and specific ways the physical properties of the cell membranes, in what can be the basis for some of their physiological actions. This paper reviews the mechanisms by which these sphingolipid signals, sphingosine and ceramide in particular, are able to modify the properties of cell membranes.