(C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Recombinant human erythropoietin (EPO) has been successfully

tested as neuroprotectant in brain injury models. The first large clinical trial with stroke patients, however, revealed negative results. Reasons are manifold and may include side-effects such as thrombotic complications or interactions with other medication, EPO concentration, penetration of the blood-brain-barrier and/or route of application. The latter is restricted to systemic Torin 1 application. Here we hypothesize that EPO is neuroprotective in a rat model of acute subdural hemorrhage (ASDH) and that direct cortical application is a feasible route of application in this injury type. The subdural hematoma was surgically evacuated and EPO was applied directly onto the surface of the brain. We injected NaCl, 200, 2000 or 20,000 IU EPO per rat i.v. at 15 min post-ASDH (400 mu l autologous venous blood) or NaCl, 0.02, 0.2 or 2 IU per rat onto the cortical surface after removal

of the subdurally infused blood t at 70 min post-ASDH. Arterial blood Selleck PSI-7977 pressure (MAP), blood chemistry, intracranial pressure (ICP), cerebral blood flow (CBF) and brain tissue oxygen (ptiO(2)) were assessed during the first hour and lesion volume at 2 days after ASDH. EPO 20,000 IU/rat (i.v.) elevated ICP significantly. EPO at 200 and 2000 IU reduced lesion volume from 38.2 +/- 0.6 mm(3) (NaCl-treated group) to 28.5 +/- 0.9 and 22.2 +/- 1.3 mm(3) (all p < 0.05 vs. NaCl). Cortical application of 0.02 IU EPO after ASDH evacuation reduced injury from 36.0 +/- 5.2 to 11.2 +/- 2.1 mm(3) (p = 0.007), whereas 0.2 IU had no effect (38.0 +/- Urease 9.0 mm(3)). The highest dose of both application routes (i.v. 20,000 IU; cortical 2 IU) enlarged the ASDH-induced damage significantly to 46.5 +/- 1.7 and 67.9 +/- 10.4 mm(3) (all p < 0.05 vs. NaCl). In order to test whether Tween-20, a solvent of EPO formulation ‘NeoRecomon (R) was responsible for adverse effects two groups were treated with NaCl or Tween-20 after the evacuation

of ASDH, but no difference in lesion volume was detected. In conclusion, EPO is neuroprotective in a model of ASDH in rats and was most efficacious at a very low dose in combination with subdural blood removal. High systemic and topically applied concentrations caused adverse effects on lesion size which were partially due to increased ICP. Thus, patients with traumatic ASDH could be treated with cortically applied EPO but with caution concerning concentration. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations.

“
“The actin cytoskeleton of plant syncytia (a multinucleate cell arising through fusion) is poorly known: to date, there have only been reports about F-actin organization in plant syncytia induced by parasitic nematodes. To broaden knowledge regarding this issue, we analyzed F-actin organization in special heterokaryotic Utricularia syncytia, which arise from maternal sporophytic tissues and endosperm haustoria. In contrast to plant syncytia induced by parasitic nematodes, Repotrectinib in vitro the syncytia

of Utricularia have an extensive F-actin network. Abundant F-actin cytoskeleton occurs both in the region where cell walls are digested and the protoplast of nutritive tissue cells fuse with the syncytium and also near a giant amoeboid in the shape nuclei in the central part of the syncytium. An explanation for the presence of an extensive F-actin network and especially F-actin bundles in the syncytia is probably that it is involved in selleck products the movement of nuclei

and other organelles and also the transport of nutrients in these physiological activity organs which are necessary for the development of embryos in these unique carnivorous plants. We observed that in Utricularia nutritive tissue cells, actin forms a randomly arranged network of F-actin, and later in syncytium, two patterns of F-actin were observed, one characteristic for nutritive cells and second-actin bundles-characteristic for haustoria and suspensors, thus syncytia inherit their F-actin patterns from their progenitors.”
“The severity of West Nile virus (WNV) infection in immunocompetent animals is highly strain dependent, ranging from avirulent to highly neuropathogenic. Here, we investigate the nature of this strain-specific restriction by analyzing the replication of avirulent (WNV-MAD78) and highly virulent (WNV-NY) strains in neurons, astrocytes, and microvascular endothelial cells,

which comprise the neurovascular unit within the central nervous system (CNS). We demonstrate that WNV-MAD78 replicated in and traversed brain microvascular endothelial cells as efficiently as WNV-NY. Likewise, similar levels of replication were detected in neurons. Thus, WNV-MAD78′s Dapagliflozin nonneuropathogenic phenotype is not due to an intrinsic inability to replicate in key target cells within the CNS. In contrast, replication of WNV-MAD78 was delayed and reduced compared to that of WNV-NY in astrocytes. The reduced susceptibility of astrocytes to WNV-MAD78 was due to a delay in viral genome replication and an interferon-independent reduction in cell-to-cell spread. Together, our data suggest that astrocytes regulate WNV spread within the CNS and therefore are an attractive target for ameliorating WNV-induced neuropathology.

In this report on our series of five patients, we describe blister-like aneurysms of the anterior communicating artery (AComA) and discuss important diagnostic and therapeutic aspects unique to them.

METHODS: In our retrospective review of 719 patients with nontraumatic subarachnoid hemorrhage admitted to our service from 1998 to 2003, 181 (25.17%) patients harbored AComA aneurysms. Five (2.76%) patients (four women, one

man) had blister-like aneurysms that were recognized at the time of surgery.

RESULTS: Initial digital subtraction angiography was diagnostic in only one patient. A second digital subtraction angiogram was diagnostic in one patient but failed to reveal an aneurysm in the remaining three patients; these were eventually diagnosed by computed tomographic angiography. All aneurysms were clipped. At the time of surgery, IWP-2 datasheet the aneurysms arose from the horizontal portion of the AComA without any involvement of the branches of the anterior cerebral artery. All presented as blister-like aneurysms that were thin-walled and lacking a surgical neck. On dissection, two of the lesions ruptured. All lesions were treated with straight fenestrated clips through the A1-AComA junction, thus remodeling the AComA. No delayed rupture was noted at the time of the last follow-up evaluation. At the time of discharge, outcomes were good in two patients, fair Dactolisib ic50 in two, and poor in the remaining patient.

CONCLUSION: Blister-like aneurysms

constitute technically challenging lesions that may occur at the AComA. Computed tomographic angiography is valuable in diagnosis. Blister-like aneurysms should be suspected when digital subtraction

angiography findings are negative for subarachnoid hemorrhage.”
“There are two major strategies to genetically modify baculoviruses. One uses a bacmid-based system which replicates in Escherichia coli using a bacterial origin of replication. The other employs a transfer vector and viral DNA which are co-transfected into insect cells and utilise host enzyme-mediated homologous recombination. Putative recombinants Dichloromethane dehalogenase are then typically screened by plaque assay. The bacmid system is more convenient, but it requires a number of complex construction and isolation steps to obtain the correct bacmid genome. Generally, the transfer vector method is preferable when only a small number of genetic modifications are required.

In this study a rapid and reliable method was developed to extract baculovirus DNA for PCR analysis from cultured insect cells. Briefly, viral DNA was isolated in three steps: SDS lysis, chloroform extraction and ethanol precipitation. The method was tested for direct screening of recombinant viruses in plaque assays. Contrary to previous reports, baculovirus DNA was isolated directly from viral plaques and successfully analysed by PCR. No prior amplification of the virus by passage in tissue culture was necessary. The major advantage of this method was a reduction in assay times from a few days to a few hours.

A regions-of-interest analysis indicated correlations between

these parameters and local activations within the left inferior frontal gyrus (IFG) such this website that lower IFG activations coincided with performance decrements.

Conclusions: Dual-task interference effects show that the production of periodically timed ankle movements, taken as modelling elements of the normal gait cycle, draws on higher-level cognitive resources involved in working memory. The interference effect predominantly concerns the timing accuracy of the ankle movements. Reduced activations within regions of the left IFG, and in some respect also within the superior parietal lobule, were identified as one factor affecting the timing of periodic ankle movements resulting in involuntary ‘hastening’ during severe dual-task working memory load. This ‘hastening’ phenomenon may be an expression of re-automated locomotor control when higher-order cognitive processing capacity can no longer be allocated to the movements due to the demands of the cognitive task. The results of our study also propose the left IFG as a target region to improve performance during dual-task walking by techniques for non-invasive brain stimulation. (C) 2013 Elsevier Ltd. All rights reserved.”
“Benzodiazepines (BZs), which are typically used as anxiolytics, act by modulating inhibitory signaling through gamma-aminobutyric acid A (GABA)(A) receptors. Functionally, the inhibitory effects

of GABA may be counterbalanced by the excitatory effects of glutamate (Glu) as the two neurotransmitter systems are metabolically linked through their synthetic intermediate https://www.selleckchem.com/products/lee011.html glutamine (Gin). The primary aim of this study was to determine whether the effects of different BZs on the GABA and Glu/Gln systems would vary according to the pharmacokinetics of the different drugs. Proton magnetic resonance spectroscopy ((1)H MRS) was used to measure GABA Glu, and Gln levels Nintedanib price in six healthy adult

volunteers 1 h and 10 h following immediate release alprazolam, extended release alprazolam, clonazepam, or placebo. Although there were no differences between 1 and 10 h when the drugs were examined individually, there was a trend level difference between the 1- and 10-h effects of BZs on Gln when the BZs were combined. In post-hoc comparisons, the difference in the Gln to creatine (Cr) ratio was 0.04 for the BZs versus placebo at 1 h and 0.01 at 10 h following the administration of drug (t(11) = 2.49, P = 0.03 1 h: t(10) = 0.65. P = 0.53 10 h; no correction for multiple comparisons). An increase in Gln/Cr at 1 h post-BZ is consistent with a functionally synergistic relationship between Glu/Gln and GABA in the brain. It also suggests that MRS may have sufficient sensitivity to detect acute drug effects. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Aims: To investigate the improved antitumour activity of SAM-3 compared with recombinant staphylococcal enterotoxins C2 (rSEC2).

Rat bladder smooth muscle cell contraction increased with larger cell populations and was inhibited by transforming growth factor-beta 1. Transforming growth factor-beta 1 induced a decrease in high molecular weight caldesmon expression in bladder smooth muscle cells.

Conclusions: Increased transforming

learn more growth factor-beta 1 expression in the detrusor of spinal cord injured rats implies up-regulation and localized signaling in response to injury. Bladder smooth muscle cells showed a loss of contractility in response to transforming growth factor-beta 1 in all cell populations. A shift in phenotype was confirmed by high molecular weight caldesmon immunostaining. These results suggest that transforming growth factor-beta 1 can modulate bladder smooth muscle cell function and may be a crucial regulator of bladder smooth muscle cell phenotype in pathological bladder conditions.”
“Visual input in the critical period is an important determinant of the functions of the visual system, affecting for example the formation of Etomoxir ic50 the ocular dominance column in the visual

cortex. The final map of columnar organization is usually determined by plastic changes in the critical period, but organization is distorted without adequate visual input. Here, we examined whether formation of the OFF-pathway dominance of P2X(2)-purinoceptor signaling in the mouse retina is the result of visual experience. The P2X(2)-purinoceptor signaling pathway developed during the critical period. However, visual experience in this period produced no plastic change in the formation of the OFF-pathway dominance of P2X(2)-purinoceptor signaling. Our findings suggest that the OFF-pathway dominance of P2X(2)-signaling in the mouse retina is intrinsically programmed. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Purpose:

Pathological alterations in the relationship between cells and the extracellular matrix have a profound effect on tissue morphology and function. Transforming growth factor-beta 1 is thought to have a role in bladder pathology by modulating the bladder smooth muscle cell phenotype and, thus, interactions with the extracellular matrix. We investigated Smoothened the effects of transforming growth factor-beta 1 on the organization of an in vitro extracellular matrix by bladder smooth muscle cells.

Materials and Methods: Rat bladder smooth muscle cells were seeded at different densities (5 x 10(4), 1 x 10(5) and 2.5 x 10(5) cells) on anchored Collagen gels and allowed to contract for 18 or 24 hours. Transforming growth factor-beta 1 effects on Collagen organization were assessed by analyzing collagen fibril orientation using small angle light scattering. Phase contrast microscopy was used to correlate changes in bladder smooth muscle cell morphology to areas of high fibril orientation. Bladder smooth muscle cells were trypsinized from the gels to confirm altered collagen architecture.

While further studies will be necessary to determine the extent to which cleavage of ICAM-5 in particular

contributes to MMP dependent LTP, our data support an emerging body of literature suggesting that MMPs are critical mediators of synaptic plasticity. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“We previously reported that HIV protease inhibitor, ritonavir, could inhibit cholesterol efflux and induce endothelial dysfunction. In this study, we further determined the effects and molecular mechanisms AZD2014 price of a clinically relevant combination of highly active antiretroviral therapy (HAART) drugs on in vitro cholesterol efflux from human macrophage-derived foam cells. Foam cells derived from human monocyte cell line this website (THP-1) and periphery blood mononuclear cells (PBMCs) treated

with HAART drugs including stavudine, didanosine and indinavir individually or in combination of three drugs (3-plex), followed by the initiation of cholesterol efflux with apolipoprotein A-I (apoA-I). Clinically relevant concentrations of HAART 3-plex significantly reduced cholesterol efflux in foam cells derived from THP-1 and PBMCs. HAART 3-plex significantly reduced the intracellular cholesterol transport molecule caveolin-1, whereas it increased superoxide anion production in THP-1 foam cells as compared with controls. Furthermore, mitochondrial membrane potential was significantly reduced, whereas the expression of NADPH oxidase subunit p67(phox) was increased in HAART 3-plex-treated macrophages. Consequently, antioxidants including ginsenosides Rb1 and Rg1, S-allyl cysteine sulphoxide (SACS), simvastatin (SVT) and vitamin E significantly abolished HAART 3-plex-induced inhibition of cholesterol efflux. Therefore, HAART drugs significantly inhibit cholesterol efflux from human macrophage-derived foam cells through downregulation of caveolin-1 and increase of oxidative stress.

Laboratory Investigation (2009) 89, 1355-1363; doi:10.1038/labinvest.2009.85; published online 21 September 2009″
“This study explored the levels of Aurora B, a key regulator of mitosis, in 71 lymph nodes and tumor specimens excised operatively from individuals with various types of non-Hodgkin lymphoma (NHLs). Immunohistochemical examination found that diffuse large B-cell lymphoma (10/21, 48%) Thymidylate synthase and Burkitt lymphoma (BL) (6/7, 86%) cells highly (percentage of positive cells, 420%) expressed Aurora B in their nuclei. On the other hand, none of the low-grade B-cell lymphoma (n = 20), except for one case of follicular lymphoma, highly expressed this protein kinase, suggesting that levels of Aurora B correlated with histological grade in B-cell NHLs (P < 0.01). Exposure of BL/leukemia cells to AZD1152-HQPA in vitro, a selective inhibitor of Aurora B kinase, potently induced growth arrest and apoptosis in a caspase-dependent, as well as -independent manner.

This network involves a set of regulated transcription factors that crosstalk with physiological signaling. The knowledge thus acquired paves the way for the genetic engineering of oilseed crops dedicated to food applications or green chemistry. (C) 2010 Elsevier Ltd. All rights reserved.”
“Objectives: AZD3965 mw Thoracic endovascular aortic repair (TEVAR) has been gaining popularity for the treatment of thoracoabdominal aortic aneurysm (TAAA). We used a nonvoluntary database to examine national trends and regional/hospital variations in the use of TEVAR and open thoracic aortic repair (OTAR) for TAAA.

Methods: From the 2005-2008 Nationwide

Inpatient Sample database, we identified all patients with the diagnosis of TAAA who were treated with TEVAR or OTAR. Rates of these procedures were compared between years, across geographic regions, and between hospitals of various bed sizes.

Results: Over the study period, the rate of OTAR remained relatively stable this website (range, 7.5/100 patients in 2005 to 10.1/100 patients in 2008; P = .26), whereas the rate of TEVAR increased dramatically (range, 1.4/100 patients in 2005 to 6.3/100 patients in 2008; P<.0001). In 2008, 29%(211) of all TEVAR procedures and 11%(130) of all OTAR

procedures were performed in western regions of the United States (P = .03). Additionally, 13%(95) of all TEVAR procedures and 3%(35) of all OTAR procedures were performed in smaller hospitals (P<.0001).

Conclusions: The use of TEVAR for TAAA repair increased significantly over the study period, whereas OTAR rates remained relatively stable. Our findings suggest that more patients who were otherwise not surgical candidates or did not have traditional

surgical indications for OTAR were treated with TEVAR, most commonly in regions or hospitals where OTAR is less often performed. Given the complexity of TAAA cases, these results may have significant HAS1 implications for patient safety in the current era of heightened health care scrutiny. (J Thorac Cardiovasc Surg 2012;144:612-6)”
“BACKGROUND

Survivors of sexual violence have high rates of depression, anxiety, and post-traumatic stress disorder (PTSD). Although treatment for symptoms related to sexual violence has been shown to be effective in high-income countries, evidence is lacking in low-income, conflict-affected countries.

METHODS

In this trial in the Democratic Republic of Congo, we randomly assigned 16 villages to provide cognitive processing therapy (1 individual session and 11 group sessions) or individual support to female sexual-violence survivors with high levels of PTSD symptoms and combined depression and anxiety symptoms. One village was excluded owing to concern about the competency of the psychosocial assistant, resulting in 7 villages that provided therapy (157 women) and 8 villages that provided individual support (248 women).

3 months.”
“Introduction Posterior putaminal atrophy, putaminal T2-hyper and/or hyposignal changes have been observed in patients with multiple system Akt inhibitor atrophy (MSA) with parkinsonism.

Methods Postmortem T2-weighted images were compared with histological findings in seven autopsy-proven cases of putaminal lesions of MSA. All cases were evaluated on 1.5T magnetic resonance imaging (MRI) scanners and three cases were evaluated on 3T scanners.

Results There were three types of putaminal changes: Type 1, mild putaminal atrophy and isointensity; Type 2, putaminal atrophy and diffuse hyperintensity with

a hyperintense putaminal rim (HPR); Type 3, putaminal atrophy and iso-or-hypointensity with HPR. The signal intensities of the putamen in Types 1 and 3 were more hypointense on 3T images than on 1.5T images. In Type 1, mild putaminal atrophy showed mild neuronal loss and gliosis and diffuse ferritin deposition. In Types 2 and 3, the areas of putaminal atrophy, severe in the posterior region, showed severe neuronal loss and gliosis, many pigments that were positive for ferritin and Fe3+ and diffuse ferritin deposition. Although, tissue rarefaction was more severe in Type 2 than in Type 3, pigment deposition was more severe in Type 3. The HPR showed a severe loss of myelin and axons with tissue

rarefaction of the AZD5363 external capsule or putaminal rim in Types 2 and 3.

Conclusion Posterior putaminal atrophy reflects neuronal loss and gliosis. While putaminal iso-or -hypointensity reflects diffuse ferritin and Fe3+ deposition, hyperintensity reflects tissue rarefaction. The HPR reflects degeneration of the putaminal lateral margin and/or external capsule. These findings reflect characteristic histological findings of MSA with parkinsonism.”
“Objectives. To validate the use of a novel mathematical algorithm applied to digital imaging and communication in medicine (DICOM) computed tomography (CT) data to automate the generation of complex endovascular graft planning.

Methods. An algorithm was developed enabling the creation of patient-specific mathematical

model based upon DICOM CT data to allow for detailed efficient geometric analysis GABA Receptor with repeatable results. This algorithm was applied to high resolution DICOM CT datasets of 15 patients, selected at random from 350 patients with aneurysms involving the visceral arteries. The longitudinal and rotational relationships of the visceral vessels were determined by the algorithm. For comparison purposes, the same measurements were acquired manually using centerline of flow software by a blinded investigator. The distance between the renal arteries, and location of the renal origins calculated with each method were then compared.

Results. Automated results were readily created for all 15 randomly selected patients.

Exclusion criteria included previously treated iliac and femoral lesions in the symptomatic leg and a body mass index >35. The operators comprised three experienced interventionalists (two vascular surgeons and an interventional radiologist) and a novice (cardiac surgeon). The primary end point of the study was to

demonstrate successful cannulation of the target vessel BTSA1 price (ie, navigation to the lesion with wire and catheter) with the Hansen VCC, with no device-related serious adverse events. Secondary end points were to assess the ability to treat lesions using the flexible catheter defined by successful insertion of a guidewire, angiography of the target vessel, delivery of balloon, and/or stent. Procedure times and radiation delivered were analyzed for the group and by operator, and t-test was performed to determine statistical significance. Complications were assessed by clinical examination and ultrasound.

Results: Lesions were successfully and safely cannulated in all limbs treated. The VCC performed as designed in all cases. All interventionalists, regardless of experience, navigated the VCC with ease. However, statistically significant differences

in navigation time and radiation per case were observed between the experienced and inexperienced interventionalists. There were no access site complications (hematoma, thrombosis, pseudoaneurysm) as evaluated by ultrasound.

Conclusions: This initial

Tariquidar in vivo experience in flexible robotics demonstrates that this technology is both efficacious and safe in the arterial tree. Although robotics provides superior maneuverability compared with current techniques, endovascular experience is crucial to taking full advantage of the extra capabilities. Valuable future considerations will include off-the-wall (center lumen) navigation with three-dimensional imaging. (J Vasc Surg 2013;57:14S-9S.)”
“Background: Both environmental and genetic factors have been reported to be involved in suicidal behaviors. Considerable evidence ADAM7 indicates that impulsive aggression is one of the important risk factors that contribute to suicide. A recent study has shown that prostaglandin E2 type 1 receptor (EP1) signaling regulates impulsive-aggressive behaviors in mice under both social and environmental stresses. To test the possible involvement of the EP1 gene in suicide, we carried out an association study of EP1 gene polymorphisms with suicide completers in the Japanese population.

Methods: We studied 5 SNPs including one SNP in exon 2 (rs3745459) and four SNPs in the potential promoter region of the EP1 gene (rs3810255, rs3810254, rs3810253 and rs10416814) in 374 healthy control and 287 completed suicide victims using standard Taqman probe genotyping assays.

It is noteworthy that the toxicity of metals does not necessarily relate to carcinogenicity in a direct manner; thus, no assumptions should be made a priori when trying to extrapolate from V(2)O(5) to other inorganic vanadium compounds. Recent studies evaluated in this review provided some further insights into possible mechanisms but do not selleck cover all relevant endpoints, address only a limited number of vanadium compounds, and have not established no-effect thresholds for carcinogenicity

or respiratory tract irritation. Thresholds need to be established in order for arguments to be made for setting a health-based OEL for non-genotoxic or secondary genotoxic carcinogens. In conclusion, important knowledge gaps preclude confident classification and risk assessment for all vanadium compounds. Evidence suggests that further research that may address some of these critical gaps is needed.”
“Earlier studies have suggested that activation of the purinergic receptor causes Na+ absorption from the endolymph through nonselective cation channels in endolymphatic sac (ES) epithelia. In

this study, the mRNA expression patterns of the P2Y(1, 2, 4, and) (6) receptors in the rat ES were examined by conventional reverse-transcription PCR. Their cellular localization was investigated by high-specificity Belinostat ic50 reverse-transcription PCR using laser capture microdissection and in-situ hybridization. Our experiments showed that the mRNA of these receptors is expressed in ES epithelia. These results indicate that extracellular nucleotides may regulate ion transport by several purinergic pathways that operate through these receptors in the ES and that some of these receptors may be responsible for regulating Na+ absorption through the activation of nonselective cation channels. NeuroReport 20:419-423 (C) 2009 Quisqualic acid Wolters Kluwer Health | Lippincott Williams & Wilkins.”
“This review provides variability

statistics for polymorphic enzymes that are involved in the metabolism of xenobiotics. Six enzymes were evaluated: cytochrome P-450 (CYP) 2D6, CYP2E1, aldehyde dehydrogenase-2 (ALDH2), paraoxonase (PON1), glutathione transferases (GSTM1, GSTT1, and GSTP1), and N-acetyltransferases (NAT1 and NAT2). The polymorphisms were characterized with respect to (1) number and type of variants, (2) effects of polymorphisms on enzyme function, and (3) frequency of genotypes within specified human populations. This information was incorporated into Monte Carlo simulations to predict the population distribution and describe interindividual variability in enzyme activity. The results were assessed in terms of (1) role of these enzymes in toxicant activation and clearance, (2) molecular epidemiology evidence of health risk, and (3) comparing enzyme variability to that commonly assumed for pharmacokinetics.