Impact of repeated nicotine and alcohol coexposure on in vitro and in vivo chlorpyrifos dosimetry and cholinesterase inhibition.

Chlorpyrifos (CPF) is an organophosphorus insecticide, and neurotoxicity results from inhibition of acetylcholinesterase (AChE) by its metabolite, chlorpyrifos-oxon. Routine consumption of alcohol and tobacco modifies metabolic and physiological processes impacting the metabolism and pharmacokinetics of other xenobiotics, including pesticides. This study evaluated the influence of repeated ethanol and nicotine coexposure on in vivo CPF dosimetry and cholinesterase (ChE) response (ChE- includes AChE and/or butyrylcholinesterase (BuChE)). Hepatic microsomes were prepared from groups of naive, ethanol-only (1 g/kg/d, 7 d, po), and ethanol + nicotine (1 mg/kg/d 7 d, sc)-treated rats, and the in vitro metabolism of CPF was evaluated. For in vivo studies, rats were treated with saline or ethanol (1 g/kg/d, po) + nicotine (1 mg/kg/d, sc) in addition to CPF (1 or 5 mg/kg/d, po) for 7 d. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), in blood and urine and the plasma ChE and brain acetylcholinesterase (AChE) activities were measured in rats. There were differences in pharmacokinetics, with higher TCPy peak concentrations and increased blood TCPy AUC in ethanol + nicotine groups compared to CPF only (approximately 1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain AChE activities after ethanol + nicotine treatments showed significantly less inhibition following repeated 5 mg CPF/kg dosing compared to CPF only (96 ± 13 and 66 ± 7% of naive at 4 h post last CPF dosing, respectively). Although brain AChE activity was minimal inhibited for the 1-mg CPF/kg/d groups, the ethanol + nicotine pretreatment resulted in a similar trend (i.e., slightly less inhibition). No marked differences were observed in plasma ChE activities due to the alcohol + nicotine treatments. In vitro, CPF metabolism was not markedly affected by repeated ethanol or both ethanol + nicotine exposures. Compared with a previous study of nicotine and CPF exposure, there were no apparent additional exacerbating effects due to ethanol coexposure.

[Urine cholinesterase activity in full-term neonatal infants with ischemic nephropathy].

To determine urine cholinesterase activity in full-term neonatal infants with varying ischemic nephropathy in an intensive care unit, the investigators studied this enzyme on days 1 and 5-7 of life, by using a kinetic photometric test optimized according to the Deutsche Gesellschaft fur Klinische Chemie (German Society for Clinical Chemistry) recommendations. In the early neonatal period, the newborns with grade III ischemic nephropathy were found to have a high urine cholinesterase activity. The determination of urine cholinesterase activity just on the first day of life may be used for the early diagnosis of grade III ischemic nephropathy in the newborns until the clinical manifestations of this pathology develop.

Investigation of the mud crab (Scylla serrata) as a potential bio-monitoring species for tropical coastal marine environments of Australia.

Mud crabs, Scylla serrata, were sampled from four estuaries (the Normanby, Herbert, Burdekin and Fitzroy Rivers) along the coast of northern Queensland, Australia, representing a pollution gradient from low to high contamination based upon previous chemical monitoring. Four biomarkers; glutathione-S-transferase (GST) activity, cholinesterase (ChE) inhibition and the urinary metabolite concentrations of naphthalene (NPH) and benzo-a-pyrene (BaP) were evaluated in S. serrata hepatopancreas, haemolymph and urine. Site-specific evidence of elevated GST activity and BaP metabolite concentrations and significant ChE inhibition was detected. Biomarker responses from this field study provide evidence of contaminant exposure of S. serrata from river estuaries along the coast of northern Queensland and indicate that further investigation is warranted. Based on the current results, and with further work on characterising the dose-response and seasonal variation in this species, mud crabs have great potential as indicator species for water quality and ecosystem monitoring programs across tropical coastal regions of Australia.

[The informational significance of metal bioaccumulation in the hair of preschool children]. / Informatsionnoe znachenie biokumuliatsii metallov v volosakh u detei doshkol'nogo vozrasta.

Hair and urine metal accumulation was studied in healthy children living in different pollution areas. The levels of biogenic amines, the activity of the enzymes LDH, AP, and cholinesterase were also determined in the exhaled air condensate (EAC) and urine. High accumulation of metals, low EAC levels of biogenic amines, high activity of the urine enzymes were observed in the children residing in high polluted areas. At the same time these changes were less marked in the moderately polluted areas. The revealed changes allow one to select children at risk and to make health-promoting measures.

Urinary cholinesterase activity is increased in insulin-dependent diabetics: further evidence of diabetic tubular dysfunction.

We measured the cholinesterase activity in morning urines from 63 insulin-dependent diabetics and 27 controls. The total esterase (TotE) activity (Ellman's method) has been divided into aliesterase (AliE), pseudocholinesterase and acetylcholinesterase by means of two inhibitors, eserine and quinidine. Diabetics were divided in 2 groups according to the urinary albumin/creatinine ratio (mg/mmol, < 2 in group 1, > 2 in group 2). The urinary cholinesterase behavior was correlated with that of a known tubular lysosomal hydrolase, N-acetyl-beta-D-glucosaminidase (NAG). Compared to normals, in addition to a significant increase in urinary NAG in diabetes (in group 2 more than in group 1), TotE and AliE were also significantly raised (+36% and 109% of the controls, in group 1 as much as in group 2).

The significance of the assays of urinary enzymes activity in patients with systemic lupus erythematosus.

The hyperexcretion of urinary enzymes with systemic Lupus Erythematosus (SLE) was assayed. 31 patients with confirmed SLE (30 women, and 1 man, age 16-33 years) were studied. Patients were divided into two groups according to the degree of kidney damage: 21 patients with proteinuria, and 10 patients without proteinuria. 12 patients of the first group had nephrotic syndrome (NS). 30 practically healthy subjects served as a control group. In patients with Lupus-nephritis (LN) the increase of activities of urinary GGT, AP, BGRS, NAG, and CHE was observed, the increase was especially clearly shown in LN-patients with NS. The increase of activity of urinary GGT and NAG was shown in the group of SLE patients who did not have clinical and laboratory signs of LN, which can be used as early index for the damage of tubular epithelium.

The rate of urinary excretion of phosalone residues in occupationally exposed persons.

The absorption of malathion and phosalone was followed in occupationally exposed workers by determination of residues excreted in the urine. Because of the high concentrations found in the morning urine samples, the rates of excretion of phosalone metabolites in the urine of a volunteer experimentally exposed to phosalone during one and then again during three subsequent working days were investigated. The urinary excretion of phosalone metabolites was most intense 4--5 hours after exposure. At the beginning of the next day, the metabolites were still well measureable in the urine. Blood and plasma cholinesterase activities were only slightly reduced during exposure. The analyses of 24-hour urine samples, or of urine samples taken 4--5 hours after exposure, are not suitable for the routine control of occupationally exposed persons because of sampling difficulties. Instead, analyses of samples taken immediately before and after work hours have to be performed. A systematic increase in the concentrations of pesticide residues in the morning urine should initiate more efficient and well-timed protection measures.

[Cholinesterase, arylesterase and proteinuria. A clinical trial in glomerular and tubular proteinuria (author's transl)]. / Cholinestérase, arylestérase et protéinuries. Essai d'application clinique dans les proteinuries glomerularires et tubulaires.

A study is presented on the activity of cholinesterase (substrate acetylcholine) and of arylesterase (substrate phenylactate) in proteinuria, classified according to the results of electrophoresis of glomerular and tubular proteinuria. Comparison is made with the corresponding serum. The urine is concentrated by dialysis on polyethylene-glycol to 60 g protein per 1000 before determination of the activities. In the presence of equal quantities of protein, cholinesterase is slightly more active in glomerular than in tubular proteinuria. In selective glomerular proteinuria, cholinesterase and arylesterase are less active than in cases with little or no selectivity. Comparison with serum, in each individual case, indicates that the ratio of activity in concentrated urine to that in serum, is higher for cholinesterase and arylesterase in tubular than in glomerular cases, whereas the reverse is true in urine at its natural concentration, on account of the lower degree of proteinuria in tubular cases. The ratio of cholinesterase to arylesterase activity in concentrated urine and serum is determined. Since cholinesterase activity is greatly increased in glomerular cases (nephrosis) this ratio is on average markedly higher in glomerular proteinuria than in serum, whereas it is similar in urine and serum of tubular cases. These results, seen in the light of the molecular weights of the enzymes, are difficult to interpret with certainty, especially as regards tubular proteinuria.

Five cases of intentional ingestion of 25 percent diazinon with treatment and recovery.

The use of atropine to block the effects of acetylcholine and pralidoxime chloride to restore cholinesterase in the blood, along with supportative therapy, intravenous fluids, and oxygen, prevented death in five cases of intentional ingestion of 25% diazinon. Treatment of such cases must be tailored to the condition of the patient, and all residual poison in the stomach must be removed as rapidly as possible with gastric lavage to prevent absorption of the poison.