In another set of experiments, the brain tissues (striatum,

In another set of experiments, the brain tissues (striatum, learn more parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[F-18]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in gamma-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken

together, these results demonstrated that 2-[F-18]fluoro-CP-118,954 specifically binds to AChE in mouse brains. (C) 2011 Elsevier Inc. All rights reserved.”
“Objective: Animal and human myocytes demonstrate significant swelling and reduced contractility during exposure to stress (metabolic inhibition, hyposmotic stress, or hyperkalemic cardioplegia), and these detrimental consequences may be inhibited by the addition of diazoxide (adenosine triphosphate-sensitive potassium channel opener) via an unknown mechanism. Both SUR1 and SUR2A subunits

have been localized to the heart, and mouse sarcolemmal adenosine triphosphate-sensitive potassium channels are composed Selleckchem 4-Hydroxytamoxifen of SUR2A/Kir6.2 subunits in the ventricle and SUR1/Kir6.2 subunits in the atria. This study was performed to localize the mechanism of diazoxide by direct probing of sarcolemmal adenosine triphosphate-sensitive potassium channel current and by genetic deletion click here of channel subunits.

Methods: Sarcolemmal adenosine triphosphate-sensitive potassium channel current was recorded in isolated wild-type ventricular mouse myocytes during exposure to Tyrode’s solution, Tyrode’s+100 mu mol/L diazoxide, hyperkalemic cardioplegia, cardioplegia+diazoxide, cardioplegia+100 mu mol/ L pinacidil, or metabolic inhibition using whole-cell voltage clamp (N = 7-12 cells per group). Ventricular myocyte volume was measured from SUR1(-/-) and wild-type mice during exposure to control solution, hyperkalemic cardioplegia, or cardioplegia+100 mu mol/ L

diazoxide (N = 7-10 cells per group).

Results: Diazoxide did not increase sarcolemmal adenosine triphosphate-sensitive potassium current in wildtype myocytes, although they demonstrated significant swelling during exposure to cardioplegia that was prevented by diazoxide. SUR1(-/-) myocytes also demonstrated significant swelling during exposure to cardioplegia, but this was not altered by diazoxide.

Conclusions: Diazoxide does not open the ventricular sarcolemmal adenosine triphosphate-sensitive potassium channel but provides volume homeostasis via an SUR1-dependent pathway in mouse ventricular myocytes, supporting a mechanism of action distinct from sarcolemmal adenosine triphosphate-sensitive potassium channel activation.

We conclude that the response

We conclude that the response LXH254 mw pattern to novel and familiar stimuli in the hippocampal region has a role in mediating differences between the

NS-ha and ns-HA temperamental profiles. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Two experiments using garden snails (Helix aspersa) showed conditioned inhibition using both retardation and summation tests. Conditioned inhibition is a procedure by which a stimulus becomes a predictor of the absence of a relevant event-the unconditioned stimulus (US). Typically, conditioned inhibition consists of pairings between an initially neutral conditioned stimulus, CS2, and an effective excitatory conditioned stimulus, CS1, in the absence of the US. Retardation and summation tests are required in order to confirm that CS2 has acquired

inhibitory properties. Conditioned inhibition has previously been found in invertebrates; however, these demonstrations did not use the retardation and summation tests required for an unambiguous demonstration of inhibition, allowing for alternative explanations. The implications of our results for the fields of comparative Aurora Kinase inhibitor cognition and invertebrate physiological models of learning are discussed.”
“The role of the purinergic system in the modulation of pain mechanisms suggests that it might be promising target for treating neuropathic pain. In this study we evaluated the effects of two different dialdehydic compounds: a modified stable adenosine (2-[1-(6-amminopurin-9-il)-2-osso-etossi]prop-2-enale, named MED1101), and oxidized ATP (Ox-ATP), in two different neuropathic pain rat models:

the sciatic spared nerve injury (SNI) and paclitaxel evoked painful peripheral neuropathy (pPPN). Neuropathic animals were divided in groups as follows: (a) treated with intraperitoneal (i.p.) MED1101 or Ox-ATP for 21 days; (b) receiving vehicle (VEH) and (c) control (CTR) rats. The allodynic and hyperalgesic behavior was investigated by Von Frey filament test and thermal Plantar test, respectively. We evaluated by immunocytochemistry the astrocytic (GFAP) and microglial (Iba1) response on lumbar spinal cord sections. In either experimental models and using either substances, treated animals showed reduced ADAM7 allodynia and thermal hyperalgesia paralleled by a significant reduction of glial reaction in the spinal cord. These data prompt to hypothesize a potential role of dialdehydes as analgesic agent in chronic neuropathic pain and a possible role as anti-gliotic molecules. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Two conditioned suppression experiments with rats were conducted to determine whether the spontaneous recovery and renewal that are commonly observed in retroactive outcome interference (e.g., extinction) also occur in retroactive cue interference. Experiment 1 showed that a long delay between Phase 2 (the interfering phase) and testing produces a recovery from the cue interference (i.e.

(C) 2008 Elsevier Inc All rights reserved “
“The heptad rep

(C) 2008 Elsevier Inc. All rights reserved.”
“The heptad repeat (HR), a conserved structural motif of class I viral fusion proteins, is responsible for the formation of a six-helix bundle structure during the envelope fusion process. The insect baculovirus F protein is a newly found budded virus envelope fusion protein which possesses common features to class I fusion proteins, such as proteolytic cleavage and the presence of an N-terminal open fusion peptide and multiple HR domains

on the transmembrane subunit F-1. Similar to many vertebrate viral fusion proteins, a conserved leucine zipper motif is predicted in this HR region proximal to the fusion peptide in baculovirus F proteins. To facilitate our understanding of the functional role of this leucine zipper-like HR1 domain Tariquidar supplier in baculovirus F protein synthesis, processing, and viral infectivity, key leucine residues (Leu209, Leu216, and Leu223) were replaced by alanine (A) or arginine (R), respectively. By using Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) as a pseudotype expression system,

we demonstrated that all mutant F proteins incorporated into budded virus, indicating that leucine substitutions did not affect intercellular trafficking of F. Furin-like protease cleavage was not affected by any of the leucine substitutions; however, the disulfide bridging and N-linked glycosylation patterns

DNA Damage inhibitor were partly altered. Single substitutions in HR1 showed that the three leucine residues were critical for F fusogenicity and the rescue of AcMNPV infectivity. Our results support the view that the leucine zipper-like HR1 domain is important to safeguard the proper folding, glycosylation, and fusogenicity of baculovirus F proteins.”
“Positron emission tomography measurements of dopaminergic D-2-like receptors may provide important insights into disorders such as Parkinson’s disease, schizophrenia, dystonia and Tourette’s syndrome. The positron emission tomography (PET) secondly radioligand [F-18](N-methyl) benperidol ([F-18]NMB) has high affinity and selectivity for D-2-like receptors and is not displaced by endogenous dopamine. The goal of this study is to evaluate the use of a graphical method utilizing a reference tissue region for [F-18]-NMB PET analysis by comparisons to an explicit three-compartment tracer kinetic model and graphical method that use arterial blood measurements. We estimated binding potential (BP) in the caudate and putamen using all three methods in 16 humans and found that the three-compartment tracer kinetic method provided the highest BP estimates while the graphical method using a reference region yielded the lowest estimates (P<.0001 by repeated-measures ANOVA). However, the three methods yielded highly correlated BP estimates for the two regions of interest.

Results: Cytotoxicity of H2O2 exposure was concentration-dependen

Results: Cytotoxicity of H2O2 exposure was concentration-dependent (30% death with 250 mu M; 87% with 500 mu M at 8 h) and time-dependent (7% at 1 h; 30% at 8 h with 250 mu M H2O2). Catalase abolished such relations. H2O2 increased PLC gamma(1) expression more than that of PLC delta(1) and almost doubled total PLC enzymatic activity between 2 and 8 h, changes prevented by catalase.

The PLC inhibitor U73112 (3 mu M) enhanced the cytotoxic concentration and time effects of H2O2. In acute studies, H2O2 rapidly caused tyrosine phosphorylation of PLC gamma(1). Conclusion: H2O2 increased SC75741 PLC gamma(1) expression and almost doubled total PLC activity, changes abolished by catalase. We conclude that H2O2 is cytotoxic to cultured VSMCs of renal preglomerular Defactinib cost arterioles, a process that is attenuated by compensatory increases in PLC gamma(1) protein level, tyrosine phosphorylation of PLC gamma(1) and PLC enzymatic activity to generate IP3. Copyright (C) 2007 S. Karger AG, Basel.”
“This study deconvolves the temporal dynamics of the neural processes underlying line bisection judgements (i.e., the landmark task).

Event-related potentials (ERPs) were recorded from 96 scalp electrodes in 10 healthy right-handed male subjects while they were judging whether horizontal lines were correctly prebisected. In the control task, subjects judged whether or not the horizontal line was transected by a vertical line, irrespective of its position. Using a current density reconstruction approach, source maxima in the time range from 50 to 400 ms after stimulus onset were

localized and the time courses of activation were elaborated. Five regions, corresponding to those revealed by our previous fMRI studies (e.g., [Fink, G. R., Marshall, J. C., Shah, N. J., Weiss, P. H., Halligan, P. W., Grosse-Ruyken, et al. (2000). Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI. Neurology, 54, 1324-1331]), were identified as contributing significant source activity related to line Aspartate bisection judgements: right middle occipital gyrus (Brodmann area; BA18); bilateral inferior occipital gyrus (BA 19); right superior posterior parietal cortex (BA7) and right inferior posterior parietal cortex (BA40). Temporal deconvolution indicated sequential activation of these regions starting at BA18 as early as 90 ms post-stimulus onset, followed by the successive activation of the right superior posterior parietal (BA7), bilateral inferior occipital (BA19) and right inferior posterior parietal cortex (BA40). Three of these areas (BA18, BA17 and BA19) became reactivated within 250 ms of stimulus onset.

The data provide evidence for an early involvement of the right hemispheric parietal network in visuo-spatial information processing.

2 (95% confidence interval, 7 0-11 4) and 7 2 (range, 2 2-25 8),

2 (95% confidence interval, 7.0-11.4) and 7.2 (range, 2.2-25.8), respectively. For benign N2 nodes, the mean and median

maximum standardized uptake values were 1.5 (95% confidence interval, 1.4-1.6) and 1.0 (range, 1.0-9.6), respectively (P < .05). When integrated fluorodeoxyglucose-positron emission tomographic/computed tomographic scans were reinterpreted by using Akt inhibitor a maximum standardized uptake value of 5.3 as a cutoff for malignancy, sensitivity decreased from 93% to 81% (P = .15), specificity increased from 86% to 98% (P < .01), positive predictive value increased from 22% to 64% (P < .01), negative predictive value was unchanged at 99%, and overall accuracy of integrated positron emission tomography/computed tomography increased from 87% to 97% (P < .01).

Conclusions: The maximum standardized uptake value is a predictor of individual VE-822 concentration lymph node metastasis in non-small cell lung cancer. Accuracy of integrated positron emission tomography/computed tomography is significantly improved by using a maximum standardized uptake value of 5.3 to assign malignancy, thereby dramatically decreasing the number of false-positive

results. More importantly, these results suggest that some patients with non-small cell lung cancer with a maximum standardized uptake value less than 5.3 in their N2 lymph nodes might be able to forego mediastinoscopy and proceed directly to thoracotomy. This represents a significant change in the current management of standardized uptake

value-positive mediastinal lymph nodes in non-small cell lung cancer.”
“Objective: The optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication.

Methods: Patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were identified. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis.

Results: From 1990 to 2006, 663 consecutive patients (538 men and 125 women) underwent resection. The median age was 63 years (range, 26-93 years). tuclazepam The operative mortality was 7% for extrapleural pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278). Significant survival differences were seen for American Joint Committee on Cancer stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P < .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001), multimodality therapy versus surgery alone (P < .001), and gender (P < .001). Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural pneumonectomy (P < .001) controlling for stage, histology, gender, and multimodality therapy.

The aim of this article is to discuss these possible future strat

The aim of this article is to discuss these possible future strategies, selleck chemicals llc focusing

in particular on those with a reasonable likelihood of a pharmaceutical product that is likely to be used clinically. Copyright (C) 2008 S. Karger AG, Basel.”
“There are several reports on the ability aphasic patients have to sing familiar songs, despite having severe speech impairments. Based on these observations it was also suggested that singing might improve speech production. However, recent experimental studies with aphasic patients found no evidence to illustrate that singing improves word production under controlled experimental conditions. This study investigated the role of singing during repetition of word phrases in a patient severely affected with non-fluent aphasia (GS) who had an almost complete lesion of the left hemisphere. GS showed a pronounced increase in the number of correctly reproduced words during singing as compared to speaking excerpts of familiar lyrics. This dissociation between singing and speaking was not seen for novel song

lyrics, regardless of whether these were coupled with an unfamiliar, a familiar, or a spontaneously generated melody during the singing conditions. These findings propose that singing might help word phrase production in at least some cases of severe expressive aphasia. However, the association of melody and text in long-term memory seems to be responsible for this effect. (C) 2008 Elsevier Ltd. All rights reserved.”
“Background/Aims: Bone marrow-derived endothelial

progenitor cells (EPCs) are believed to contribute to endothelial repair after vascular ABT-737 in vitro damage. To investigate the potential for microvascular repair in patients with ANCA-associated vasculitis (AAV), we conducted a cross-sectional study determining the number of circulating EPCs in patients with AAV, chronic uremia, atherosclerosis, and in healthy volunteers. Methods: The number of circulating EPCs was determined by colony-forming assay in 41 patients with AAV, 15 hemodialysis Orotic acid patients (without vasculitis), 13 patients with peripheral arterial occlusive disease (PAOD), and 25 healthy controls. Results: Patients with AAV had a significantly lower number of CFU-Hill than healthy subjects (median 0.3 vs. 19.5 CFU-Hill/ml blood, p < 0.0001), but not than patients on hemodialysis or with PAOD. Neither institution of treatment nor entering remission increased the number of EPCs in AAV patients. The number of EPCs did not correlate with markers of disease activity. AAV patients with glomerular filtration rate <15 ml/min had an even lower number of circulating EPCs than patients with better preserved renal function (median 0.05 vs. 1.2 CFU-Hill/ml, p = 0.015) and patients with anti-MPO positivity had a trend towards a higher number of EPCs than patients with anti-PR3 antibodies (median 3.1 vs. 0.18 CFU-Hill/ml, p = 0.06).

Duration of HB reflex (T-apnoe) was continuously reduced as body

Duration of HB reflex (T-apnoe) was continuously reduced as body temperature rose during experiment. Compared to normothermic controls, animals with fever had significant shortening of T-apnoe at 240 min and 300 min after LPS administration. Fever was further accompanied by a reduction

in the strength of HB reflex (inhibitory ratio, IR). In comparison with controls, significant decrease of IR was observed at 300 min after LPS injection. Conclusion: altered neural control of breathing selleck compound demonstrated by decreased power of Hering-Breuer inflation reflex in conditions of LPS-induced fever may facilitate thermal tachypnoea and/or play a role in the origin of respiratory instability accompanying febrile response. (C) 2012 Published by Elsevier Ltd.”
“To the Editor: Katz et al. (May 2 issue)(1) assessed functional outcomes of meniscectomy versus physical therapy in patients with a meniscal tear and osteoarthritis. The primary outcome was the change in the Western Ontario and McMaster Universities

Osteoarthritis Index (WOMAC) physical-function score, and a secondary outcome was pain. But in efforts to assess the benefits of an intervention aimed at restoring meniscal function, more specific tools for meniscectomy, such as the Lysholm score(2) or the International Knee Documentation Committee (IKDC) score,(3) would appear to have been more appropriate. Second, osteoarthritis was defined according to the radiography-based criteria of Kellgren …”
“Macrophage migration inhibitory factor (MIF) was the original C59 wnt mw cytokine, ifenprodil described almost 50 years ago and has since been revealed to be an important player in pro-inflammatory diseases. Recent work using MIF mouse models has revealed new roles for MIF. In this review, we present an increasing body of evidence

implicating the key pro-inflammatory cytokine MIF in specific biological activities related directly to cancer growth or contributing towards a microenvironment favouring cancer progression.”
“Environmental factors play an important role in the seasonal adaptation of body mass and thermogenesis in small, wild mammals. To determine the contributions of photoperiod and cold on seasonal changes in energy metabolism and body mass, the resting metabolic rates (RMR), nonshivering thermogenesis (NST), energy intake and gut morphology of the tree shrews were determined in winter and summer and in laboratory acclimated animals. Body mass, RMR and NST increased in winter, and these changes were mimicked by exposing animals to short-day photoperiod or cold in the animal house. Energy intake and digested energy also increased significantly in winter, and also during exposure of housed animals to both short-day photoperiod and cold. The lengths and weights of small intestine increased in winter.

These findings support the contention that drugs and food are par

These findings support the contention that drugs and food are part of the same category of primary reinforcers, whereas money is discounted differently, as a conditioned reinforcer.”
“Contextual change or constancy between occasions of memory formation and retrieval are commonly assumed to affect retrieval success, yet such effects may be inconsistent, and the processes leading to the pattern

of effects are still not well understood. We conducted a systematic investigation of environmental context effects on memory, using a range of materials (common objects, pictures of familiar and unfamiliar faces, words, and sentences), and four types of retrieval (free recall, cued recall, recognition, and order memory), all assessed Evofosfamide within participants. Additionally, we examined the influence of mnemonic challenge on context effects by examining both healthy participants and a group of patients in rehabilitation following traumatic brain injury (TBI). We found no effects of contextual factors on tests of recognition for either group of participants, but effects did emerge for cued and free recall, PLX4032 chemical structure with the most prominent effects being on memory for objects. Furthermore, while patients’ memory abilities in general were impaired relative to the comparison group, they exhibited greater influences of contextual reinstatement on several recall tasks. These Sulfite dehydrogenase results support suggestions

that environmental context effects on memory are dependent on retrieval mode and on the extent to which

retrieval is challenging because of neurocognitive status. Additionally, findings of environmental context effects in memory-impaired TBI patients suggest that by harnessing such preserved indirect memory (e.g., using reminder technologies), it may be possible to ameliorate TBI patients’ difficulties in explicit remembering.”
“English words with an inconsistent grapheme-to-phoneme conversion or with more than one pronunciation (homographic heterophones; e.g., lead-/l epsilon d/, /lid/) are read aloud more slowly than matched controls, presumably due to competition processes. In Japanese kanji, the majority of the characters have multiple readings for the same orthographic unit: the native Japanese reading (KUN) and the derived Chinese reading (ON). This leads to the question of whether reading these characters also shows processing costs. Studies examining this issue have provided mixed evidence. The current study addressed the question of whether processing of these kanji characters leads to the simultaneous activation of their KUN and ON reading, This was measured in a direct way in a masked priming paradigm. In addition, we assessed whether the relative frequencies of the KUN and ON pronunciations (dominance ratio, measured in compound words) affect the amount of priming.

157; 95% CI limits, 0 033-0 737) Taking percutaneous coronary in

157; 95% CI limits, 0.033-0.737). Taking percutaneous coronary intervention out of the calculation model, this positive effect was no longer significant (OR, 0.344; CI, 0.091-1.298). Logistic regression for perioperative MACCE, with as well as without percutaneous coronary intervention as a confounder, also showed a significant positive effect of preoperative coronary stenting (OR, 0.231; 95% CI, 0.091-0.590).

Conclusions: check details Coronary stenting before CAGB in diabetic patients does not predispose to a higher perioperative risk regarding mortality and morbidity after CABG surgery. (J Thorac Cardiovasc Surg 2011;142:e53-7)”
“Rationale

Alterations in the activity of the prefrontal and orbitofrontal cortices of cocaine addicts have been linked with re-exposure to cocaine-associated stimuli.

Objectives Using an animal model of relapse to cocaine seeking, the present study investigated the expression patterns of four different activity-regulated genes within prefrontal cortical brain regions after 22 h or 15 days of abstinence during context-induced relapse.

Materials find more and methods Rats self-administered cocaine or received yoked-saline for 2 h/day for 10 days followed by 22 h or 2 weeks of abstinence when they were re-exposed to the self-administration

chamber with or without levers available to press for 1 h. Brains were harvested and sections through the prefrontal cortex were processed for in situ hybridization using radioactive oligonucleotide probes encoding c-fos, zif/268, arc, and bdnf.

Results Re-exposure

to the chamber in which rats previously self-administered cocaine but not saline, regardless of lever availability, increased the expression of all genes in the medial prefrontal and orbitofrontal cortices at both time points with one exception: bdnf mRNA was significantly increased in the medial prefrontal cortex at 22 h only if levers previously associated with cocaine delivery were available to press. Furthermore, re-exposure of rats to the chambers in which they received yoked saline enhanced both zif/268 and arc expression selectively 3-oxoacyl-(acyl-carrier-protein) reductase in the orbitofrontal cortex after 15 days of abstinence.

Conclusions These results support convergent evidence that cocaine-induced changes in the prefrontal cortex are important in regulating drug seeking following abstinence and may provide additional insight into the molecular mechanisms involved in these processes.”
“Sixteen organic co-solvents were screened for stereoselective reduction of 1-acetonapthone in aqueous media by whole cells of Geotrichum candidum. Benzyl alcohol was found to be a good co-solvent as it afforded a high coversion and reduced deactivation of the cells. Half-lives of the wet and lyophilized whole cell biocatalysts in pure benzyl alcohol were 23.07 and 11.21 hours, respectively.

We hypothesize that both mechanisms exist, and further that previ

We hypothesize that both mechanisms exist, and further that previous demonstrations of lip-reading functional activations in Broca’s region and the posterior planum temporale reflect the sensory-motor mechanism. We tested one prediction of this hypothesis using fMRI. We assessed whether viewing visual speech

(contrasted with facial gestures) activates the same network as a speech sensory-motor integration task (listen to and then silently rehearse speech). Both tasks activated locations within Broca’s area, dorsal premotor cortex, and the posterior planum temporal (Spt), and focal regions of the STS, all of which have previously been implicated in sensory-motor integration for speech. This finding is consistent with the view that visual speech influences heard speech

via sensory-motor networks. Lip-reading also activated a much wider network in the superior temporal lobe than the sensory-motor task, possibly reflecting a more direct cross-sensory integration network. (c) 2009 Elsevier Ireland Ltd. All rights reserved.”
“The routine use of tobacco products may modify key metabolizing systems, which will further impact the metabolism of environmental contaminants. The objective of this study was to quantify the effect of repeated in vivo exposures to nicotine, a major pharmacologically active component of cigarette smoke, on in vitro metabolism of chlorpyrifos (CPF). CPF is an organophosphorus (OP) insecticide that is metabolized by cytochrome P-450 (CYP450) to its major metabolites, chlorpyrifos-oxon (CPF-oxon) and 3,5,6-trichloro-2-pyridinol (TCP). Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg for 1, 7, or 10 d. Rats were sacrificed

4 or 24 h after the last nicotine treatment, and liver microsomes were prepared. The microsomes were incubated with varying concentrations of CPF and the production of the metabolites CPF-oxon and TCP were measured. The metabolism of CPF to the active oxon metabolite did not show significant changes following repeated nicotine treatments, evidenced by the unchanged pseudo first-order clearance rate of Vmax/Kmapp. The Vmax describing the metabolism of CPF to the inactive metabolite, TCP was increased in 24-h postdosing groups, after both single and repeated treatments of nicotine. In contrast, the metabolism to TCP was unchanged in groups evaluated at 4 h (single or repeated) post nicotine dosing. Some basic marker substrate activities were also investigated to ensure that nicotine exerted effects on CYP450 activities. Total P450 reduced spectra were not altered by nicotine treatment, but marker substrate activities for CYP1A and CYP2E1 were increased at 24 h after the single treatment, and marker substrate activity for CYP2B was decreased 4 h after 7 d of treatment.