Maturational differences in chlorpyrifos-oxonase activity may contribute to age-related sensitivity to chlorpyrifos

Chlorpyrifos (CPF), a commonly used cholinesterase-inhibiting insecticide, is lethal at much lower doses to young animals than adults. To explain this higher sensitivity in younger animals, we hypothesized that young rats have less chlorpyrifos-oxonase (CPFOase) activity than adults. To test this hypothesis, CPFOase activity was measured in the brain, plasma, and liver of male, postnatal day 4 (PND4) and adult (PND90) Long-Evans rats. CPFOase is biochemically defined as a Ca(2+)-dependent A-esterase that hydrolyzes chlorpyrifos-oxon (CPFO), the active metabolite of CPE. No brain CPFOase activity was detected at either age. Plasma and liver CPFOase activities were markedly lower at PND4 compared to adult: PND4 plasma and liver CPFOase activities were 1/11 and 1/2 the adult plasma and liver activities, respectively. Because the Km of CPFOase activity was high (i.e., 210-380 microM), it was important to determine if this CPFOase activity could hydrolyze physiologically relevant concentrations (i.e., nM to low microM) of CPFO. This was accomplished by comparing the shifts in the tissue acetylcholinesterase (AChE) IC50 for CPFO in the presence or absence of CPFOase activity. One would expect an increase in the "apparent" IC50 if CPFOase hydrolyzes substantial amounts of CPFO during the 30 minutes the tissue is preincubated with the CPFO. In the adult, both plasma and liver AChE apparent IC50 values were higher in the presence of CPFOase activity, suggesting that the CPFOase in those tissues was capable of hydrolyzing physiologically relevant concentrations of CPFO within 30 minutes. In young animals, however, there was less of a shift in the IC50 curves compared to the adult, confirming that the young animal has less capacity than the adult to detoxify physiologically relevant concentrations of CPFO via CPFOase.     

Analysis of failures and poor results of lumbar spine surgery

The failures and poor results of lumbar spine surgery are analyzed in a retrospectively study of 105 consecutive patients referred to the authors for evaluation during 1976. Those who had a history of industrial or vehicular accident outnumbered others by about two to one. Review of histories, physical findings, and myelograms in most of the patients failed to substantiate the diagnosis of ruptured disc or nerve root compression. Many of the failures occurred in thos patients in whom little if any evidence of nerve root compression was found. The indications for surgery were poor in this group. Other failures occurred in patients who had improper, incomplete, or inadequate operations, especially those with lumbar spondylosis, a retained fragment of disc, or surgery at the wrong level. In addition to failure, poor results were recorded in patients who had significant nerve root or cauda equina injury from surgery, associated "arachnoiditis" which is thought to result from surgical trauma in many instances, or multiple operations leading to a hopelessly disabled state.     

Protein-bound carbohydrates in breast cancer. Liquid-chromatographic analysis for mannose, galactose, fucose, and sialic acid in serum

We describr high-resolution chromatographic analysis for protein-bound sialic acid in serum, with use of a cerate oxidimetric detector. Values for sera from normal women averaged 680.5 mg/liter, with a coefficient of variation of 23%. Including data obtained by previously developed chromatographic procedures for protein-bound mannose, galactose, and fucsoe, we assessed sera from breast-cancer patients whose malignancy had been categorized as either stable, responsive, or progressive (based on clinical observations spaced from two to five months apart). All of 12 responsive patients had decreases of protein-bound fucose averaging 34.5% (SD, 16.1) and all of 10 patients with progressive disease had increases averaging 38.3% (SD 21.5). Changes in fucose averaged less than 6.7% (SD, 4.9) for eight patients with clinically stable breast cancer. Changes in protein-bound mannose, galactose, and sialic acid did not correlate as well as did fucose with the clinical disease status of the patients.     

Monoamine acid metabolites in ventricular CSF of patients with brain tumours

Homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in ventricular CSF were determined in 19 patients (12 female 7 male) with brain tumours. No relationship was found between ventricular fluid pressure (VFP) and levels of HVA and 5-HIAA. A relationship was observed between ventricular CSF, HVA concentrations and tumour induced alterations in CSF dynamics. HVA concentrations were very high in patients whose tumours involved the third ventricle, the aqueduct, or the fourth ventricle, producing marked alterations in CSF flow. HVA concentrations significantly lower than in controls were observed in cases where tumours involved the lateral ventricles. Concentrations of acid metabolites in patients with little or no alteration in CSF dynamics corresponded with those in patients with other neurosurgical disorders.     

Insulin-like actions of nickel and other transition-metal ions in rat fat-cells

NiC12 (1-6mM) decreased adrenaline and glucagon-stimulated lipolysis in rat fat-cells, and also considerably stimulated [U-14C]glucose incorporation into fat-cell lipids. 2. These insulin-like effects were also observed with CuCl, CuCl2, CoCl2 and (to a lesser extent) with MnCl2. 3. NiCl2 was less effective in mimicking insulin effects on [U-14C]fructose metabolism than on glucose utilization. 4. It is tentatively suggested that these transition-metal ions may mimic actions of insulin at the fat-cell plasma membrane which decrease lipolysis and stimulate glucose transport, but do not mimic certain other effects of the hormone on intracellular metabolic processes. 5. These results are discussed with reference to suggestions that redistributions of cellular Ca2+ are associated with insulin action in fat-cells.     

Addition of guar gum and soy protein increases the efficacy of the American Heart Association (AHA) step I cholesterol-lowering diet without reducing high density lipoprotein cholesterol levels in non-human primates

The aim of this study was to determine whether the addition of soy protein and guar gum to the American Heart Association (AHA) Step I diet would increase its efficacy compared with the typical "Average American Diet" (AAD) in a non-human primate model. Twenty adult female cynomolgus monkeys (Macaca fascicularis) were fed one of three diets for 6 wk. The AAD contained 36% energy from fat; the standard Step I diet contained 30% energy from fat; and the modified AHA Step I diet contained 30% energy from fat with the addition of soy protein isolate (10% of total energy) and guar gum (5.8 g/d). Plasma samples were collected from food-deprived monkeys at 4, 5 and 6 wk of dietary treatment for analyses of plasma total cholesterol (TC), lipoprotein cholesterol and triacylglycerol (TAG) concentrations. Plasma TC, LDL-C, HDL-C and TAG concentrations were not significantly different in wk 4, 5 and 6 within any of the diet periods; thus the three measurements were averaged. After 6 wk of dietary treatment, monkeys fed the standard Step I diet had lower plasma TC (-19%) (P < 0.05) and LDL cholesterol (LDL-C) (-24%) (P < 0.09) than when they were fed the AAD, with no effect on HDL cholesterol (HDL-C), the lipoprotein cholesterol profile or TAG. Beyond the effect of the standard Step I diet, the modified AHA Step I diet further reduced plasma TC and LDL-C (-24% and -40%) (P < 0. 05) and the TC/HDL-C and LDL-C/HDL-C ratios (-37% and -52%) (P < 0. 05) with no significant changes in plasma HDL-C or TAG. The primary conclusions of this study are that the efficacy of the AHA Step I cholesterol-lowering diet can be increased with the addition of soy protein and guar gum and provide a more favorable lipoprotein cholesterol profile. Whether the cholesterol-lowering effect is the result of soy protein or guar gum or a synergistic effect of both remains to be determined.