Neurological effects of acute exposure to caffeine and organophosphates in mice.

Organophosphate (OP) pesticides are commonly known for their neurotoxicity. In the current experiments, two OPs used agriculturally, chlorpyrifos and dimethoate, were separately adminis- tered with centrally acting caffeine that is known to affect the pharmacological action of other substances. The aim of this study was to determine whether the combination of OP and caffeine may influence their neurotoxic potential. For this purpose, some neurobehavioral effects of this concomitant exposure were assessed in adult Swiss mice. All substances were given intra- peritoneally (i.p.) as single injections. In the passive avoidance task, chlorpyrifos (100 mg/kg) administered together with caffeine (40 mg/kg) significantly impaired acquisition. In the rota-rod test, the addition of caffeine at doses of 20 and 40 mg/kg, induced motor coordination impairment in chlorpyrifos (100 mg/kg)-treated mice. Neurobehavioral impairments were not observed for caffeine, chlorpyrifos and dimethoate (50 mg/kg) given separately as well as for the combina- tion of dimethoate and caffeine. Chlorpyrifos (100 mg/kg) alone and in combination with caffeine (40 mg/kg) significantly reduced acetylcholinesterase (AChE) activity. The current study shows that concomitant exposure to caffeine and chlorpyrifos can cause neurotoxic effects in mice despite the absence of these effects when caffeine and chlorpyrifos are administered alone. How- ever, the possible mechanisms involved need further investigations.

Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia.

OBJECTIVES: Osteoporosis is a skeletal disorder characterized by impaired bone turnover and compromised bone strength, thereby predisposing to increased risk of fracture. Preclinical research has shown that compounds produced by the olive tree (Olea europaea), may protect from bone loss, by increasing osteoblast activity at the expense of adipocyte formation. The aim of this exploratory study was to obtain a first insight on the effect of intake of an olive extract on bone turnover in postmenopausal women with decreased bone mass (osteopenia). DESIGN AND SETTING: For that, a double blind, placebo-controlled study was performed in which participants were randomly allocated to either treatment or placebo groups. PARTICIPANTS: 64 osteopenic patients, with a mean bone mineral density (BMD) T-score between -1.5 and -2.5 in the lumbar spine (L2-L4) were included in the study. INTERVENTION AND MEASUREMENTS: PARTICIPANTS received for 12 months daily either 250 mg/day of olive extract and 1000 mg Ca (treatment) or 1000 mg Ca alone (placebo). Primary endpoints consisted of evaluation of bone turnover markers. Secondary endpoints included BMD measurements and blood lipid profiles. RESULTS: After 12 months, the levels of the pro-osteoblastic marker osteocalcin were found to significantly increase in the treatment group as compared to placebo. Simultaneously, BMD decreased in the placebo group, while remaining stable in the treatment group. In addition, improved lipid profiles were observed, with significant decrease in total- and LDL-cholesterol in the treatment group. CONCLUSION: This exploratory study supports preclinical observations and warrants further research by showing that a specific olive polyphenol extract (Bonolive®) affects serum osteocalcin levels and may stabilize lumbar spine BMD. Moreover, the improved blood lipid profiles suggest additional health benefits associated to the intake of the olive polyphenol extract.

Day/night ratio of microproteinuria and blood pressure rhythm in type II diabetes.

The paper discusses the results of the studies conducted with a group of patients with type II diabetes without clinical nephropathy. The aim of the study was to attempt to determine the markers for early stages of diabetic nephropathy in NIDDM patients. The following examinations were carried out: the level of selected microproteinuric components, 24 h monitoring of arterial blood pressure, and electrocardiogram (ECG). Among the patients examined, the level of alfa-1-microglobulin, albumin and immunoglobulin G (IgG) in diabetic patients was higher than in the control group, and the increased activity of beta NAG was observed. The 24 h profile of blood pressure and the ratio afternoon/night of albumin excretion flattened in the majority of diabetic patients. The results of the study suggest that the proximal tubules and the membranes of renal glomeruli are damaged as early as during the period of subclinical diabetic nephropathy.

Neurotoxic effect of dermally-applied chlorpyrifos and cypermethrin in Wistar rats.

The aim of the study was to evaluate the neurotoxic effect of a dermally-applied mixture of chlorpyrifos and cypermethrin in rats based on cognitive function, activity of the blood cholinesterase and brain acetylcholinesterase, as well as histologic brain examination. Nurelle D 550 EC (500 g of chlorpyrifos and 50 g of cypermethrin) was used in the study. The application liquid was in the form of a water solution. The investigation covered eight groups of animals: six experimental groups and two control groups, of 15 rats each. Experimental groups received 5.6 mg/cm2 chlorpyrifos and 0.5 mg/cm2 cypermethrin, or 27.8 mg/cm2 chlorpyrifos and 2.7 mg/cm2 cypermethrin dermally, for one day, one week and four weeks, except for Saturdays and Sundays. The preparations examined were applied to the tail skin of rats. The animals were anaesthetized at the end of exposure period. Plasma cholinesterase and brain acetylcholinesterase activities were determined. The brain for histological examination was perfused with a solution of methanol, formalin and glacial acetic acid, and the sections stained by the Nissel method. The behaviour of the animals was evaluated in the open field test four times: before exposure, and after one, two and four weeks of the experiment. The results of the study showed that chlorpyrifos and cypermethrin applied in a mixture caused an inhibition of cholinesterase and acetylcholinesterase activity and elicited the pycnosis of brain neurocytes.

[Microproteinuria and circadian rhythm of blood pressure in patients with arterial hypertension]. / Mikroproteinuria i rytm dobowy cisnienia u pacjentów z nadcisnieniem tetniczym.

Microproteinuria is a recognized sign of early nephropathy in the course of arterial hypertension. There is few data concerning the excretion of proteins other than albumin in this group of patients. The aim of the study was to examine circadian rhythm of alfa-l-microglobulin (AlMG), albumin (ALB), immunoglobulin G (IgG) excretion and N-acetyl-beta-glukosaminidase (beta NAG)-activity, then to compare the results with the results of 24 hour ambulatory monitoring of arterial blood pressure in patients with arterial hypertension. The study comprised 28 patients. The control group included 27 healthy volunteers. Albumin concentration was determined by Beckman ICS2 nephelometer, using Beckman and Dako reagents. Blood pressure and ECG were monitored by analysis with ABP-system (AMP-USA). In patients with arterial hypertension significantly higher levels of ALB, AlMG, IgG and increased beta NAG activity were observed in morning urine samples. Despite hypotensive treatment blood pressure values were slightly, though significantly higher than in the control group. Among patients in the study circadian BP rhythm was disturbed. The results obtained suggest that in this group of patients subclinical nephropathy develops involving renal glomeruli and proximal tubules--probably resulting from vascular and humoral disorders, with accompanied hypertension.

Particular fractions of microproteinuria in patients with stabile angina pectoris and without a clinical nephropathy.

The determination of microalbuminuria is a valuable method in the diagnosis of renal and vascular diabetes or hypertension complications. Recently, microalbuminuria appeared to be the predictor of coronary heart diseases (CHD). The presented study comprised 26 patients with stable angina pectoris (AP) and 27 healthy volunteers. We simultaneously evaluated microproteinuria during the first morning and afternoon miction and the 24-h blood pressure. Amongst patients with AP all urine protein concentrations were increased (results in g/mol creatinine): alpha-1-microglobulin (1.04 + 0.13 vs. 0.47 + 0.05, p < 0.001) albumin (0.95 + 0.15 vs. 0.61 + 0.05, p < 0.05) and IgG (1.00 + 0.17 vs. 0.55 + 0.05, p < 0.01) were higher, in comparison to control group values. Indices for diurnal blood pressure rhythm were significantly lower in the AP group for both systolic (1.07 + 0.01 vs. 1.14 + 0.01 p < 0.001) and diastolic (1.09 + 0.02; vs. 1.21 + 0.03 p < 0.01) pressures. A physiological increase of albumin from the afternoon sample was only observed in the control group. Thus, our AP patients demonstrated signs of subclinical nephropathy in both the proximal tubuli and glomeruli.