Toxicokinetics of Nickel in Mice Studied with the {gamma}-Emitting Isotope 57Ni

The -emitting isotope ⁵⁷Ni was generated in a cyclotron to allowwhole-body counting of laboratory animals dosed with nickel.⁵⁷NiCl₂ was administered either orally by gastric intubationor by intraperitoneal injection to groups of mice in doses equivalentto the average human daily dietary nickel intake per mass unit.When given orally, the whole-body retention (WBR) was 0.02–0.36%of the administered dose at 45–75 hr. When given intraperitoneally,the WBR was 1–6% at 20–50 hr. After adjustment forthe rapid excretion of systemic nickel, the intestinal absorptioncould be estimated to be 1.7–10%. The relative WBR didnot vary with the magnitude of the dose within 0.05–5µmol Ni/kg given orally or 0.005–0.5 µmol/kggiven intraperitoneally. At 8 hr, the tissue concentration washighest in the kidneys, followed by the carcass, lungs, testicles,liver, and the spleen. After 20 hr, the highest concentrationswere still found in the kidneys followed by the lungs, the liver,and the carcass. At 20 hr after oral administration, 50–70%of ⁵⁷Ni retained in the body was within the carcass. The secondhighest nickel content was found in the kidneys, followed bythe liver and lungs. Whereas nickel in the kidneys was rapidlyexcreted, the elimination from the lungs and liver was relativelyslow, thereby, after 40 hr, resulting in a higher nickel contentin the liver than that in the kidneys. When nickel was givenintraperitoneally, practically no nickel was transported viathe portal vein to the liver after 20 hr, resulting in a lownickel content in the liver and a higher content in the kidney.These results document that the use of ⁵⁷Ni for studies on nickeltoxicokinetics is feasible and useful, and that the method isespecially well suited for comparative studies with a durationof up to 6 days.     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.     

Positive and negative consequences of alcohol drinking among young university students in Finland

In a sample of 1663 female and 707 male Finnish university students in their first study year, the female students reported less negative and less positive consequences of alcohol drinking than their male counterparts. The female students also drank less, less frequently and less often for intoxication. However, the profile of negative and positive consequences of drinking was similar for both genders; 74.6% of the female students and 80.0% of the males had more positive than negative experiences from alcohol. Both the positive and negative consequences of drinking correlated positively to alcohol consumption and drinking for intoxication. About half of the students who had many positive consequences of drinking were not heavy drinkers and did not report many negative consequences. Depression, anxiety, stress or psychosomatic symptoms did not correlate with either with positive or negative consequences of drinking, nor with alcohol consumption. Drinking for anxiety, depression, stress or the reduction of tension appeared to be infrequent. Young Finnish university students mostly drink for the positive consequences of drinking.     

Radionuclide Angiocardiography in Post-myocardial Infarction Patients

ABSTRACT One hundred and one representative post-myocardial infarction (MI) patients were investigated with radionuclide angiocardiography (RNA) and exercise test within 1 month of the MI and after 6 and 12 months. From the RNA were calculated the left ventricular ejection fraction (LVEF) and a quantified phase image, the phase standard deviation (phase-SD), representing the timing of the left ventricular contraction. The mean phase-SD was significantly higher among these patients (18°, 19° and 18°, respectively, at the three investigations) compared to phase-SD in normals (6°), indicating an impaired timing of the left ventricular (LV) contraction. At all three investigations a significant correlation was found between the phase-SD and the LVEF (r=0.58, r=-0.74 and r=-0.75, respectively) and the corrected QT interval (r=0.27, r=0.44 and r=0.39, respectively). Maximal serum ASAT in patients with their first MI correlated significantly to phase-SD. Low exercise capacity or unfavourable NYHA classification was associated with high phase-SD. Phase-SD higher than mean was also associated with significantly increased mortality during the follow-up year (P=0.0057). In conclusion, phase-SD, reflecting the timing of the LV contraction wave, is easily accessible and clinically relevant. It merits further investigation as a prognostic factor after an MI.     

Real‐time multiplex PCR assay for detection of Yersinia pestis and Yersinia pseudotuberculosis

A multiplex real‐time polymerase chain reaction (PCR) assay was developed for the detection of Yersinia pestis and Yersinia pseudotuberculosis. The assay includes four primer pairs, two of which are specific for Y. pestis, one for Y. pestis and Y. pseudotuberculosis and one for bacteriophage λ; the latter was used as an internal amplification control. The Y. pestis‐specific target genes in the assay were ypo2088, a gene coding for a putative methyltransferase, and the pla gene coding for the plasminogen activator. In addition, the wzz gene was used as a target to specifically identify both Y. pestis and the closely related Y. pseudotuberculosis group. The primer and probe sets described for the different genes can be used either in single or in multiplex PCR assays because the individual probes were designed with different fluorochromes. The assays were found to be both sensitive and specific; the lower limit of the detection was 10–100 fg of extracted Y. pestis or Y. pseudotuberculosis total DNA. The sensitivity of the tetraplex assay was determined to be 1 cfu for the ypo2088 and pla probe labelled with FAM and JOE fluorescent dyes, respectively.     

Seroprevalence of pertussis antitoxin (anti‐PT) in Sweden before and 10 years after the introduction of a universal childhood pertussis vaccination program

Hallander HO, Andersson M, Gustafsson L, Ljungman M, Netterlid E. Seroprevalence of pertussis antitoxin (anti‐PT) in Sweden before and 10 years after the introduction of a universal childhood pertussis vaccination program. APMIS 2009; 117: 912–22. The prevalence of IgG ELISA antibodies against pertussis toxin (anti‐PT) was studied in two Swedish seroepidemiological studies. One was performed in 1997 when the new pertussis vaccination program was 1 year old (n = 3420). In 2007, when Pa vaccines had been used countrywide for 10 years in the universal child vaccination program, this study was repeated to analyze the effect of vaccination on anti‐PT prevalence (n = 2379). Before the statistical analysis of seroprevalence, children vaccinated within the last 2 years before the serosurveys were excluded. The results indicate a reduced exposure to Bordetella pertussis in the population. The proportion of sera without measurable anti‐PT antibodies increased significantly, aggregated over all comparable age groups, from 3.8% in people sampled in 1997 to 16.3% in people sampled in 2007. For cord blood, 1% was without measurable anti‐PT antibodies in 1997 compared to a significantly higher level, 12%, in 2007. With anti‐PT concentrations of ≥50 and ≥100 EU/ml as cutoff points for ‘recent infection’ the proportion above the cutoff points for younger children was significantly higher in 1997 than in 2007 at both cutoff points. For all adults, 20 years of age and older, the difference in proportions above the lower cutoff point was close to statistically significant, comparing 1997 with 2007. This was not the case at 100 EU/ml. In the 1997 samples of children, there was a significant downward trend of ‘recent infections’ at both cutoff points for three sampled age groups between 5 and 15 years of age from 21% at 5.0–5.5 years of age to 7% at 14.7–15.7 years for the lowest cutoff. In the 2007 samples of children, on the contrary, there was a significant continuous upward trend of ‘recent infections’, at both cutoff points, for four sampled age groups between 4 and 18 years of age – from 4% at 4–5 years of age to 16% at 17–18 years at the lowest cutoff. The continuous increase, with age of children with high anti‐PT concentrations, supports the recent change in the general Swedish childhood vaccination program to include a pre‐school booster at 5–6 years and a school‐leaving booster at 14–16 years of age.     

Solid-phase synthesis and conformational studies of helper T cell immunogenic peptides that carry carbohydrate haptens linked to serine

N ^α-Fmoc serine and its corresponding pentafluorophenyl ester were glycosylated with the 1,2-trans peracetates of the disaccharides galabiose and cellobiose. Complete stereoselectivity and 52-75% yields were obtained under boron trifluoride etherate promotion. Lower yields and loss of stereoselectivity were obtained when thioglycosides. trichloroacetimidates or glycosyl bromides were employed as glycosyl donors. The glycosylated building blocks were used in solid-phase synthesis of derivatives of a helper T cell immunogenic peptide consisting of amino acids 52-61 from hen-egg lysozyme. ¹H-NMR spectroscopy in DMSO-d₆ showed that the peptide moiety of the glycopeptides assumed random conformations which were not influenced by glycosylation at different positions.     

Microvascular response to local application of dequalinium chloride

Dequalinium chloride is a topical antiseptic, whose use may be attended by skin necrosis. Since microcirculatory changes are an early and distinct manifestation of tissue injury, the tissue damaging effect of dequalinium chloride on the microcirculation was examined. The immediate vascular reactions were studied by vital microscopy, of the hamster cheek pouch and the late effects were visualized by microangiography of the rabbit ear. An aqueous solution of dequalinium chloride in concentrations well below those used in clinical practice induced severe microcirculatory disturbances.     

Anxiety in adolescents born preterm or with very low birthweight: a meta‐analysis of case–control studies

Aim To determine if adolescents who are born very preterm (<32wks; of gestation) and/or with very low birthweight (VLBW; <1500g) have a higher risk of experiencing clinically significant anxiety problems. Method We used a systematic review and meta‐analysis. We searched the databases ISI Web of Knowledge, PubMed, PsycNET, Educational Resources Information Center (ERIC), Latin American and Caribbean Literature on the Health Sciences (LILACS), and Virtual Health Library (VHL) with equivalent search expressions (from the databases’ inception to June 2011). Also, we screened reference lists of identified articles. We selected case–control studies of adolescents 11 to 20 years old who were very preterm/VLBW and had a matched reference group born at term with normal birthweight that reported a validated anxiety outcome measure. For data extraction, two authors independently reviewed titles, abstracts, and full articles identified through the searches. Subsequently two authors independently extracted data. Results We included six studies with 1519 adolescents (787 very preterm/VLBW, 732 comparisons). The general risk of developing clinically significant anxiety problems was nearly doubled (p<0.05) in the very preterm/VLBW population (OR 2.27, 95% confidence interval 1.15–4.47). The overall prevalences were 9.9% in the very preterm/VLBW group and 5.5% in the comparison group. Interpretation Those born very preterm/VLBW have an increased risk of developing clinically significant anxiety problems in adolescence.