The association of adolescents' smoking with the physical activity levels of their friends.

BACKGROUND: Smoking is inversely related to people's Physical Activity Level (PAL). As the behavior of friends may affect the choices and behavior of adolescents, having friends with a high PAL may potentially protect against adolescent smoking. This study aims to assess whether adolescents' smoking is associated with the PAL of their friends. METHODS: SILNE-R survey data of 11.918 adolescents from 55 different schools in 7 European cities was used to determine weekly smoking, individual PAL, PAL of friends, school PAL, and smoking of friends. Multilevel, multivariable logistic regression analysis were used to assess the association between the PAL of friends and weekly smoking. Several socio-demographic variables were included as covariates in the analysis. RESULTS: Our results indicated that 10.8% of the respondents was smoking weekly. Weekly smoking was most common among adolescents whose friends had a PAL of 0-42.0 min per day (14.5%). Respondents were significantly more likely to be smoking weekly if their friends were on average 0-42 min vs. 80-180 min physically active (OR 1.27 [95% CI 1.04-1.55]). This association existed independently of the individual PAL of respondents. Stratification for smoking of friends yielded equal results, although the association appeared to be somewhat stronger for those with smoking friends (OR 1.38 [95% CI 1.06-1.82]). CONCLUSION: Adolescents are less likely to smoke weekly if they associate with friends who spend >80 min per day on physical activity. Initiatives aimed at the prevention of smoking among adolescents may benefit from organizing group-based physical activity programs.

Nicotine dependence among adolescents in the European Union: How many and who are affected?

BACKGROUND: Nicotine dependence during adolescence increases the risk of continuing smoking into adulthood. The magnitude of nicotine dependence among adolescents in the European Union (EU) has not been established. We aimed to estimate the number of nicotine dependent 15-year-old adolescents in the EU, and identify high-risk groups. METHODS: The number of nicotine dependent 15-year-olds in the EU was derived combining: (i) total number of 15-year-olds in the EU (2013 Eurostat), (ii) smoking prevalence among 15-year-olds (2013/2014 HBSC survey) and (iii) proportion of nicotine dependent 15-year-olds in six EU countries (2013 SILNE survey). Logistic regression analyses identified high-risk groups in the SILNE dataset. RESULTS: We estimated 172 636 15-year-olds were moderately to highly nicotine dependent (3.2% of all 15 years old; 35.3% of daily smokers). In the total population, risk of nicotine dependence was higher in males, adolescents with poor academic achievement, and those with smoking parents or friends. Among daily smokers, only lower academic achievement and younger age of smoking onset were associated with nicotine dependence. CONCLUSION: According to our conservative estimates, more than 172 000 15-year-old EU adolescents were nicotine dependent in 2013. Prevention of smoking initiation, especially among adolescents with poor academic performance, is necessary to prevent a similar number of adolescents getting addicted to nicotine each consecutive year.

Effect of tryptophan-N-formylated gramicidin on growth of Plasmodium berghei in mice.

The effect of tryptophan-N-formylated gramicidin (NFG) on the growth of Plasmodium berghei in mice was tested in three different experiments. NFG was shown to be capable of inhibiting the growth of the parasite in a dose-dependent way, although its action did not result in elimination of the parasite and was only temporary, preventing mice from early death, presumably due to cerebral malaria, but not from fatal generalized malaria. Intriguingly, a similar observation was made with two other drugs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, an inhibitor of viral and eukaryotic DNA polymerases, and the presumed topoisomerase II inhibitor, a bisquaternary quinolinium salt. A rise in the level of parasitemia after 8 days, despite continued treatment, was not due to parasite-induced reticulocytosis, as demonstrated in experiments in which this condition was induced artificially. NFG was added in the form of lipid vesicles in which the peptide had been incorporated. The inhibitory action of NFG was not modulated by the lipid composition of the vesicles. Control experiments did not demonstrate any toxicity of NFG when it was administered in lipid vesicles. The main observation is that NFG is able to inhibit the growth of a malaria parasite in vivo at concentrations that are well tolerated by the host.

Tryptophan-N-formylated gramicidin causes growth inhibition of Plasmodium falciparum by inducing potassium efflux from infected erythrocytes.

In a study of the supposed selective action of tryptophan-N-formylated gramicidin (NFG) on infected erythrocytes as well as the relationship between the ability of NFG to inhibit parasite growth and its capacity to induce potassium leakage from infected cells, a series of experiments was performed in which in vitro cultures of Plasmodium falciparum were incubated with NFG or gramicidin. Those cultures were subsequently assayed for intracellular sodium and potassium contents, cell lysis, and/or parasite viability. It is shown and discussed that although NFG can attack both infected and uninfected erythrocytes, resulting in potassium efflux from and sodium influx into these cells, the effects are much greater on infected erythrocytes than on uninfected ones. Furthermore, the results strongly suggest that NFG-mediated potassium efflux is the direct cause of parasite death.

Effects of gramicidin and tryptophan-N-formylated gramicidin on the sodium and potassium content of human erythrocytes.

In order to get a better understanding in the mechanism by which tryptophan-N-formylated gramicidin (NFG) and gramicidin kill the malaria parasite Plasmodium falciparum in vitro, we studied the capacity of these peptides to change the potassium, as well as the sodium, composition of normal human erythrocytes, and their ability to cause cell lysis. It is shown that both peptides are able to induce potassium leakage from, and sodium flux into, erythrocytes in such a manner that it is most likely that they are able to form cation channels in the membrane of these cells. For both peptides, potassium efflux proceeds at a faster rate than sodium influx, but this difference is greater for NFG than for gramicidin. This explains the observation that gramicidin is more lytic than NFG is, even when comparing concentrations that show the same antimalarial activity. The finding that gramicidin is approximately 10 times more active than NFG in causing potassium efflux from normal erythrocytes, as well as in killing the malaria parasite, supports the hypothesis that peptide-induced parasite death is related to their capacity to induce potassium leakage from infected erythrocytes. Finally, the observation that erythrocytes are able to restore their normal ion contents after losing more than 50% of their potassium content by incubation with NFG or gramicidin, suggests that, in vivo, and upon treatment with drug concentrations that cause full inhibition of parasite growth, these cells would not be irreversibly damaged by action of the drugs.

Stage-dependent effects of analogs of gramicidin A on the growth of Plasmodium falciparum in vitro.

Tryptophan-N-formylated gramicidin A, a nonhemolytic derivative of the toxic peptide antibiotic gramicidin A, has previously been shown to induce potassium leakage from Plasmodium falciparum-infected erythrocytes in vitro and to inhibit the growth of the parasite. In the present study the antimalarial activities of two other nonhemolytic derivatives of gramicidin A, viz., acylated gramicidin A and desformylated gramicidin A, were tested and compared with those of gramicidin A and tryptophan-N-formylated gramicidin A. The 50% growth-inhibitory concentrations (IC50 values) of the four compounds varied from 0.3 to 18.3 nM, and complete growth inhibition was detected within one parasitic growth cycle. Using highly synchronized cultures of P. falciparum, it was furthermore shown that the gramicidin analogs are inhibitory to all developmental stages of the parasite, although their efficiency in accomplishing growth inhibition was found, as expected, to be clearly stage-dependent and to increase with the age of the parasite.

Arginine 53 is involved in head-group specificity of the active site of porcine pancreatic phospholipase A2.

The X-ray structure of a mutant porcine pancreatic phospholipase A2 inhibitor complex [Thunnissen et al. (1990) Nature 347, 689-691] has been determined. This structure shows several interactions between the sn-2-acyl chain and the phosphate moiety of the inhibitor at sn-3 and the protein. The interactions of the remaining part of the polar head group are less clear. Because Arg53 is in close proximity to the head group, we tested the importance of charge at position 53 on enzymatic activity and specificity. Arg53 has been replaced by a glutamine and a glutamic acid in mutants R53Q and R53E, respectively. The effects of the mutations were tested with both zwitterionic and anionic substrates. With monomeric, zwitterionic, (R,S)-1,2-dihexanoyldithiopropyl-3-phosphocholine as substrate, the mutants R53Q and R53E display twofold and sevenfold, respectively, increased kcat/Km values, composed of increased kcat and decreased Km values. Tested on micelles of zwitterionic (R)-1,2-dioctanoylglycero-3-phosphocholine the mutants R53Q and R53E are more active than the native enzyme, whereas these mutations have an opposite effect on the activity on anionic (R)-1,2-dioctanoylglycero-3-phosphoglycol. Thus, whereas the native enzyme is 0.3 times as active on zwitterionic as on the anionic substrate, these ratios are 1.0 (R53Q) and 1.7 (R53E) for the mutants. No changes in activity were observed with the anionic substrate (R)-1,2-dioctanoylglycero-3-sulfate. Binding studies with substrate-derived inhibitors confirmed the increased affinity for zwitterionic phospholipids and the reduced affinity for anionic phospholipids. The kinetic and binding data indicate the involvement of the charge of residue 53 in head-group specificity and suggest a position of residue 53 closer to the choline or glycol than to the phosphate.

Muscular changes in the guinea pig caused by chronic ascorbic acid deficiency.

The present study was undertaken in order to decide whether chronic ascorbic acid (AA) deficiency only causes myopathy in the guinea pig or whether it also causes central nervous system pathology. Juvenile male animals, fed an optimally balanced, purified diet with minimal amounts of AA, developed a nutritional myopathy complicated by trauma, arthrogenic factors and defective repair. The absence of changes in the spinal pyramidal tracts, the anterior horn cells and peripheral nerve agrees with the absence of neurogenic changes in muscle specimens as target, targetoid, or small angulated fibers, group atrophy, type grouping, or changes in the distribution pattern of fibers. We conclude that chronic AA deficiency in the guinea pig cannot serve as an animal model of human amyotrophic lateral sclerosis.

Intraperitoneal infusion of EDTA in the rat blocks completely the prolactin rise in the plasma during suckling.

Lactating rats supplied with chronically indwelling intravenous (i.v.) and intraperitoneal (i.p.) catheters were allowed to suckle after a night of isolation from their offspring. The effect of infusions of saline and EDTA, given i.v. or i.p. on the suckling-induced rise of plasma prolactin was evaluated by radioimmunoassay. i.v. saline and EDTA did not affect the normal prolactin rise induced by suckling. However, i.p. EDTA completely blocked this rise, while the weight gain of the pups during the suckling period was only slightly depressed. i.p. EDTA had no suppressive effect on the perphenazine-induced rise of plasma prolactin and caused only a moderate inhibition of the prolactin rise in the plasma evoked by thyrotropin-releasing hormone and by brief exposure to ether. The experiments indicate, that because i.p. EDTA probably stimulates dopamine only slightly, it must inhibit prolactin secretion via another mechanism. This study, therefore, strongly supports the idea that more than one hypothalamic factors affect prolactin release during suckling.