Bacterial reduction of N-oxides of tobacco- specific nitrosamines (TSNA)

1 Contrary to established metabolic pattern, a recent investigation of NNK metabolism produced in rat urine higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyri dyl)-1-butanol (NNAL) than their N-oxides, suggesting that reconversion of N-oxides could occur after urine formation. 2 To verify the possible role of bacteria in the reduction of NNK-N-oxide and NNAL-N-oxide to their respective parent compounds, NNK and NNAL, in smokers with urinary tract infection (UTI), the N-oxides were isolated from the urine of rats treated with 5-3HNNK and individually incubated at 37°C with ten bacterial species in sterile human urine under different pH regimens. After incubation with the bacteria, aliquots of culture media were analyzed by high pressure liquid chromatography (HPLC) with radiochemical detection. 3 Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Proteus mirabilis possessed varying capacity to regenerate NNK and NNAL from their N- oxides while others showed no detectable reductive capability within 24 h. 4 This result constitutes the first experimental evidence that in tobacco users with concomitant UTI, bacterial regeneration of the procarcinogenic NNK and NNAL from their N-oxides could occur in the bladder leading to increased carcinogen burden in these individuals

Kaon-nucleon couplings for weak decays of hypernuclei

We investigate the weak kaon-nucleon (NNK) S-wave and P-wave interactions using heavy baryon chiral perturbation theory. The leading 1-loop SU(3) breaking contributions to the ppK, pnK, and nnK couplings are computed. We find that they suppress all NNK amplitudes by 30\% to 50\%. The ratio of neutron-induced to proton-induced hypernuclear decay widths is sensitive to such reductions. It has been argued that the discrepancy between the predicted and observed P-wave amplitudes in \Delta s=1 hyperon decay results from an accidental cancellation between tree-level amplitudes, and is not a fundamental problem for chiral perturbation theory. Agreement between experimentally determined NNK P-wave amplitudes and our estimates would support this explanation

CBERN - Naskapi Projects

The Canadian Business Ethics Research Network (CBERN) began working in collaboration with the Naskapi Nation of Kawawachikamach (NNK) in early 2007. This relationship was initiated by former NNK Chief Phil Einish. The goal was to ensure that the Naskapi people benefited from mining on their traditional territories and avoided the negative impacts caused by previous mining activity by the Iron Ore Company of Canada.Funding Program: SSHRC Insight Grant Funding Amount: $469,23

Agonist and antagonist effects of tobacco-related nitrosamines on human α4β2 nicotinic acetylcholine receptors

Regulation of the ‘neuronal’ nicotinic acetylcholine receptors (nAChRs) is implicated in both tobacco addiction and smoking-dependent tumor promotion. Some of these effects are caused by the tobacco-derived N-nitrosamines, which are carcinogenic compounds that avidly bind to nAChRs. However, the functional effects of these drugs on specific nAChR subtypes are largely unknown. By using patch-clamp methods, we tested 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) on human α4β2 nAChRs. These latter are widely distributed in the mammalian brain and are also frequently expressed outside the nervous system. NNK behaved as a partial agonist, with an apparent EC50 of 16.7 μM. At 100 μM, it activated 16 % of the maximal current activated by nicotine. When NNK was co-applied with nicotine, it potentiated the currents elicited by nicotine concentrations ≤ 100 nM. At higher concentrations of nicotine, NNK always inhibited the α4β2 nAChR. In contrast, NNN was a pure inhibitor of this nAChR subtype, with IC50 of approximately 1 nM in the presence of 10 μM nicotine. The effects of both NNK and NNN were mainly competitive and largely independent of Vm. The different actions of NNN and NNK must be taken into account when interpreting their biological effects in vitro and in vivo

Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN

Tobacco use is a major public health problem worldwide. Tobacco-related cancers cause millions of deaths annually. Although several tobacco agents play a role in the development of tumors, the potent effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are unique. Metabolically activated NNK and NNN induce deleterious mutations in oncogenes and tumor suppression genes by forming DNA adducts, which could be considered as tumor initiation. Meanwhile, the binding of NNK and NNN to the nicotinic acetylcholine receptor promotes tumor growth by enhancing and deregulating cell proliferation, survival, migration, and invasion, thereby creating a microenvironment for tumor growth. These two unique aspects of NNK and NNN synergistically induce cancers in tobacco-exposed individuals. This review will discuss various types of tobacco products and tobacco-related cancers, as well as the molecular mechanisms by which nitrosamines, such as NNK and NNN, induce cancer

Renormalization factor and effective mass of the two-dimensional electron gas

We calculate the momentum distribution of the Fermi liquid phase of the homogeneous, two-dimensional electron gas. We show that, close to the Fermi surface, the momentum distribution of a finite system with $N$ electrons approaches its thermodynamic limit slowly, with leading order corrections scaling as $N^{-1/4}$. These corrections dominate the extrapolation of the renormalization factor, $Z$, and the single particle effective mass, $m^*$, to the infinite system size. We show how convergence can be improved analytically. In the range $1 \le r_s \le 10$, we get a lower renormalization factor $Z$ and a higher effective mass, $m^*>m$, compared to the perturbative RPA values.Comment: 4 pages, 3 figure

Asymptotics in randomized urn models

This paper studies a very general urn model stimulated by designs in clinical trials, where the number of balls of different types added to the urn at trial n depends on a random outcome directed by the composition at trials 1,2,...,n-1. Patient treatments are allocated according to types of balls. We establish the strong consistency and asymptotic normality for both the urn composition and the patient allocation under general assumptions on random generating matrices which determine how balls are added to the urn. Also we obtain explicit forms of the asymptotic variance-covariance matrices of both the urn composition and the patient allocation. The conditions on the nonhomogeneity of generating matrices are mild and widely satisfied in applications. Several applications are also discussed.Comment: Published at http://dx.doi.org/10.1214/105051604000000774 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org