Pentobarbital in tobacco.

The spectrometric analysis of extracts from tobacco and tobacco smoke revealed the presence of pentobarbital in the analyzed substances. Tobacco samples and tobacco smoke were extracted with chloroform, determinations were performed with the Perkin-Elmer Autosystem XL system, on a Turbo Mass spectrometer. Subject to analysis were 4 cigarette brands manufactured in Poland and raw, unprocessed tobacco. The presence of pentobarbital in the analyzed samples was confirmed by the analysis of the mass spectrum of the substance, as well as by comparison of retention time with standard of pentobarbital. The determined pentobarbital concentrations in tobacco amounted to 3-6 microg/cigarette, and in tobacco smoke they were approximately 45% lower. In case of tobacco extracts it can with high probability be excluded that pentobarbital is synthesized during chromatographical analysis. The presence of pentobarbital in tobacco is thus beyond question.     

Pharmacokinetics of phenazone after bilateral ovariectomy in female rabbits]

The aim of this study was to evaluate the influence of female sex hormones on phenazone pharmacokinetics using as an experimental model female rabbits after a bilateral ovariectomy. Eighteen female rabbits divided into two groups: control animals and experimental rabbits, that underwent ovariectomy, were used in the study. Pharmacokinetic assays were performed in all animals: prior to the study, after 1 month and after 2 months. Blood was sampled within 24 hours after intragastric administration of phenazone at a dose 50 mg/kg b.w. Two compartment open model was used for calculations. Significant increase in AUC and prolongation of phenazone halflife as well as a decrease in the total body clearance were noted. The study demonstrated the possible inhibition of the microsomal mixed-function oxidase system by oestrogens.     

Neuropathological Effects of Triphenyl Phosphite on the Central Nervous System of the Hen (Gallus domesticus)

The neurotoxic effects of single subcutaneous injections of1000 mg triphenyl phosphite (TPP)/kg body weight were investigatedin White Leghorn hens. At 7 days postexposure, birds began toshow signs of mild to moderate ataxia that progressed to severeataxia and paralysis at 21 days. Inhibition of whole brain neuropathytarget esterase was 85% at 48 hr and 73% by 21 days postexposure.After postexposure periods of 7, 14, and 21 days, hens werekilled and their brains and spinal cords were examined for degeneratingaxons and terminals using the Fink-Heimer silver impregnationmethod. A small amount of degeneration was noted at 7 days.By 21 days, dense degeneration was noted in the spinal graymatter and funiculi. Degeneration was also present in the granularcell layer of cerebellar folia I-VI and in nuclei and fibertracts of the medulla. Moderate to dense degeneration was alsoseen in several forebrain and midbrain areas including the paleostriatum,ansa lenticularis, the dorsointermediate thalamic nucleus, lateralspiriform, pedunculopontine tegmental, and lateral mesencephalicnuclei and in the deeper layers of the optic tectum. These resultsindicate that, in addition to affecting the spinal cord andbrainstem, exposure to TPP also damages higher order centersresponsible for processing and integrating sensorimotor, visual,and auditory information.     

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

The behavioural, but not the hypothermic or corticosterone, response to 8-hydroxy-2-(DI-n-propylamino)-tetralin, is antagonized by NAN-190 in the rat

The 5-HT1A receptor antagonistic properties of 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl] piperazine (NAN-190) were studied in rats: its effect on the 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced behavioural syndrome (flat body posture and reciprocal forepaw treading), hypothermia and secretion of corticosterone, i.e. responses mediated by 5-HT1A receptors, were examined. The drug NAN-190 (1-8 mg/kg) antagonized dose-dependently behavioural effects of 8-OH-DPAT (in both non-reserpinized and reserpine-pretreated animals); however, when administered in doses of 0.5-4 mg/kg, it did not affect the hypothermic or the hormonal response to 8-OH-DPAT. However, NAN-190 (1-8 mg/kg) given alone, produced hypothermia and increased the concentration of corticosterone in serum. The latter effects of NAN-190 were not reduced by (-)pindolol or spiperone. Moreover, the NAN-190-induced secretion of corticosterone was not affected by ketanserin, prazosin or yohimbine. The above results indicate that NAN-190 acts as a 5-HT1A receptor antagonist, only in the model of the 8-OH-DPAT-induced behavioural syndrome. The lack of effect of NAN-190 on the hypothermic or corticosterone response to 8-OH-DPAT most probably results from its own action which mimics the effects of 8-OH-DPAT. The mechanisms responsible for the NAN-190-induced hypothermia and secretion of corticosterone are still unknown, though stimulation of 5-HT1A receptors (either effect), 5-HT2 receptors and alpha 1- and alpha 2-adrenoceptors (corticosterone response) seems to be excluded.     

Pyridinium crosslinks of collagen as a marker of bone resorption rates in children and adolescents: Normal values and clinical application

The aim of our study was to establish normal values of urinary pyridinoline (Pyr) and deoxypyridinoline (DPyr) excretion for children aged 3–18 years, examine the biological variability of the marker, and assess its clinical value for pediatric patients with growth hormone deficiency. Pyr and DPyr was measured in first void urine samples from 692 healthy subjects (340 boys, 352 girls) by high-performance liquid chromatography. At sampling, age, body height, and weight was recorded for all individuals. Short-term variability in crosslinks excretion was examined in four healthy children. The clinical value of the marker was studied in seven patients with growth hormone (GH) deficiency. In childhood, crosslinks excretion exceeded normal adult values by about fivefold and declined during puberty. In the age range of 13–18 years, gender-related differences in Pyr and DPyr levels were observed, presumably resulting from the earlier onset of puberty in girls. Urinary levels of Pyr and DPyr were highly correlated both in males and females. Pyr/DPyr ratio was significantly higher in adolescents than children, suggesting enhanced release of Pyr from extraosseous sources. In both genders, neither age nor anthropometric variables showed a linear effect on crosslinks excretion. The range of within-subject, short-term variability in urinary Pyr and DPyr was relatively high (CV: 6%–21%), indicating that single measurements of crosslinks excretion may not adequately reflect bone resorption rates in children. Pyr and DPyr levels were significantly lower in GH-deficient patients and normalized during human growth hormone (hGH) therapy. Significant correlations between growth velocity (GV) and crosslinks levels were found, but individual prediction of GV increment during hGH treatment may be inaccurate. Pyr/DPyr ratio was not related to GV. It is concluded that measurement of urinary Pyr and DPyr excretion in children may be a valuable tool to assess bone resorption rates in population-based studies. In individual patients, however, only qualitative evaluation of disease severity and response to treatment seems justified.     

Cholesterol screening: observed cholesterol reduction in a prospective study in Norway

The general public of the City of Bergen, Norway was Invitedto participate in a cholesterol screening programme in October1988. Participants received the results of the cholesterol screeningand nutritional information from trained health personnel. Ashort questionnaire was mailed to all 354 participants 1–2weeks after the initial cholesterol screening. In March 1990,all participants were invited to have their cholesterol levelsre-examined. Psychosocial factors believed to be predictiveof future serum cholesterol changes were assessed at baselinealong with demographic variables. The majority of participants(61%) reduced their cholesterol level from October 1988 to March1990, and the average reduction in cholesterol level for thetotal population was 4.0%. Baseline cholesterol levels, beingconfident of one's own ability to change one's diet (self-efficacy),seeing heart disease risk reduction as very important, and maritalstatus were factors that significantly predicted successfulcholesterol reduction 18 months later.     

The effect of sulphinpyrazone and alpha-tocopherol on platelet activation and function in haemodialysed patients

In 30 patients on chronic haemodialysis treatment the platelet activity and function were studied before and during antiplatelet therapy with alpha-tocopherol and sulphinpyrazone. In both kinds of treatment a significant decrease of ADP-induced and spontaneous aggregation was observed. Sulphinpyrazone exerts an inhibitory effect not only on platelet aggregation but also on platelet factor 3 and provokes a significant prolongation of the bleeding time.