Children's diets,pesticide uptake,and implications for risk assessment: An Israeli case study

The presence of pesticides in the Israeli food supply is well documented but little is known about the risks posed by children's diets for potential exposures. We investigated potential exposures to food-borne pesticides in a sample of 301 urban Israeli children (2008–10). Data from a food frequency questionnaire, 24 hour food recall, and Israel's national pesticide monitoring program were used to estimate uptake factors for 26 compounds in 27 fruits and vegetables. A pilot risk assessment was performed and the findings were compared with the Israel Ministry of Health's 2012 pesticide risk assessment for the general population. The surveyed children had higher potential exposures than the general population for over one third of the compounds, and uptake factors exceeded the Acceptable Daily Intake in ten compounds. Methamidophos, exceeded the ADI at the 25th percentile and fenamiphos, iprodione, and oxydemethon methyl, exceeded the ADI at the 50 percentile. ADIs for several compounds were exceeded even though the residues detected were below the statutory limit. Improved monitoring, enforcement, and revision of the Maximum Residue Limit for certain food/pesticide pairs are indicated as is the need to incorporate data on children's actual food consumption in national risk assessments.     

Regulation of neurotransmitter enzyme by quisqualate subtype glutamate receptors in cultured cerebellar and hippocampal neurons

The possible involvement of ionotropic and metabotropic quisqualate (QA) receptors in neuronal plasticity was studied in cultured glutamtergic cerebellar or hippocampal cells in terms of the specific activity of phosphate-activated glutaminase, an enzyme important in the synthesis of the putative neurotransmitter pool of glutamate. When cerebellar of hippocampal neurons were treated with QA, it elevated the specific activity of glutaminase in a dose-dependent manner. The half-maximal effect was obtained at about 0.1 μM, the maximum increase was at about 1 μM, but levels higher than 10 μM QA produced progressive reduction in glutaminase activity. In contrast, QA had little effects on the activities of lactate dehydrogenase and aspartate aminotransferase and the amount of protein, indicating that the increase in glutaminase was relatively specific. The QA-mediated increase in glutaminase was mimicked by the ionotropic QA receptor agonist -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; EC₅₀, about 0.5 μM), but not by the metabotropic QA receptor agonist trans-(±)-1-aino-cyclopentyl-1,3,dicarboxyalte (t-ACPD; up to 0.5 mM). The specific ionotropic QA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited QA- and AMPA-mediated increases in glutaminase activity in a dose-dependent manner, whereas other glutamate receptor antagonists, -2-amino-5-phosphonovalerate, γ- -glutamyl aminomethyl sulphonic acid and γ- -glutamyl diethyl ester were ineffective. The elevation of neurotransmitter enzyme was Ca²⁺-dependent. The increase in Ca²⁺ influx essentially through the activation of L-type voltage-operated Ca²⁺ channels, and not the mobilization of internal Ca²⁺ stores, was responsible for these QA receptor-mediated long-term plastic changes in hippocampal and cerebellar neurons.     

Regional differentiation of sympathetic activity during hypothalamic heating and cooling in anesthetized rabbits

Summary In anesthetized rabbits immobilized with succinyl choline, the discharges of sympathetic efferents supplying cutaneous and visceral regions were simultaneously recorded. The effects of thermal stimulation of the hypothalamic region were tested on the basis of the integrated discharges. During hypothalamic heating cutaneous sympathetic activity decreased, corresponding to increased ear blood flow, while visceral sympathetic activity increased. During hypothalamic cooling there was, on the average, no significant change of regional sympathetic activity. However, in single experimental periods an increase of cutaneous and a decrease of visceral sympathetic activity was found.The observed responses of regional sympathetic activity were compared with findings about regional cutaneous and intestinal blood flow under the same thermal stimulus and further with corresponding former investigations on regional blood flow and regional sympathetic activity during spinal thermal stimulation. It is suggested by this comparison that regional differentiation of sympathetic activity represents a specific thermoregulatory response of the vasomotor system mediated by the hypothalamic thermoregulatory center.     

Reflex increases in heart-rate induced by perfusing the hind leg of the rat with solutions containing lactic acid

The hypothesis that metabolic receptors in skeletal muscle influence heart-rate during exercise was tested by means of a perfused preparation of the rat's hind legs. The isolated leg was connected to the body only by nerve and bone and was perfused with tyrode solution. The humoral changes of exercise were simulated by perfusing with modified tyrode solutions in which concentration of K⁺, osmolality, concentrations of lactic acid, and inorganic phosphate were changed to reflect to those occurring during heavy exercise. Only perfusion with a solution enriched with lactic acid elicited a significant increase in heart-rate. The response disappeared when the nerve supply to the leg was cooled or sectioned. 20–60 s after the start of perfusion with solution of high [lactic acid] heart-rate began to increase reaching a maximum ( ± SE = 20.2 ± 8.2,n = 7) after about 2 min. The effect on heart-rate increased when the venous concentration of lactic acid was increased the range from 3 to 10 mmol/l. In further experiments, we tried to separate the effects of pH and lactate. Heart-rate responses were induced only at low pH and at low pH the extent to which heart-rate changed increased with increases in lactate concentration.     

Ethinyl estradiol treats collagen-induced arthritis in DBA/1LacJ mice by inhibiting the production of TNF-alpha and IL-1beta

We previously demonstrated the therapeutic effects of ethinyl estradiol (EE), an orally active estrogen and a component of birth control pills, in encephalitogenic autoimmune encephalomyelitis (EAE). In this study, we report the effectiveness of EE in treating collagen-induced arthritis (CIA) induced with bovine type II collagen (bCII) in DBA/1LacJ mice, a CIA susceptible strain. Both low and high doses of EE notably suppressed clinical and histological signs of CIA in a dose-dependent manner compared to vehicle-treated controls. Oral treatment with EE decreased proliferation and secretion of pro-inflammatory factors, TNF-alpha IFN-gamma, MCP-1 and IL-6 by bCII peptide-specific T cells, production of bCII-specific IgG2a antibodies, and mRNA for cytokines, chemokines and chemokine receptors in joint tissue. This is the first report demonstrating effective treatment of joint inflammation and clinical signs of CIA with orally administered ethinyl estradiol, thus supporting its possible clinical use for treating rheumatoid arthritis in humans.     

A biological context for the self-nonself discrimination and the regulation of effector class by the immune system

An effective immune response to an antigen requires two sets of decisions: Decision 1, the sorting of the repertoire, and Decision 2, the regulation of effector class. The repertoire, because it is somatically generated, large, and random, must be sorted by a somatic mechanism that subtracts those specificities (anti-self) that, if expressed, would debilitate the host, leaving a residue (anti-nonself) that, if not expressed, would result in the death of the host by infection. The self-nonself discrimination is the metaphor used to describe Decision 1, the sorting of the repertoire. In order to be functional, the sorted repertoire must be coupled to a set of biodestructive and ridding effector functions, such that the response to each antigen is treated in a coherent and independent manner. Although a reasonably complete framework for Decision 1 exists, Decision 2 lacks conceptualization. The questions that must be considered to arrive at a proper framework are posed. It should be emphasized that manipulation at the level of Decision 2 is where clinical applications are likely to be found.     

Cloning,sequencing and analysis of the yeastS. uvarum ERG10 gene encoding acetoacetyl CoA thiolase

Summary TheERG10 gene specific toS. uvarum, a brewing yeast, has been cloned by complementation of anS. cerevisiae erg10 mutant.S. uvarum contains two differentERG10 genes. One of these is similar to theS. cerevisiae ERG10 gene; they are structurally different, but functionally homologous. The clonedERG10 gene has been located on chromosome XVI, and we have shown that it is allelic to the previously isolatedtsm0115 mutants. Northern blot and sequence analysis indicate that theERG10 gene is highly expressed, and biochemical and genetic evidence show that it encodes the cytoplasmic acetoacetyl CoA thiolase.