Prolonged, physiologically relevant nicotine concentrations in the airways of smokers.

Nicotine from cigarette smoke is a biologically active molecule that has pleiotropic effects in the airway, which could play a role in smoking-induced lung disease. However, whether nicotine and its metabolites reach sustained, physiologically relevant concentrations on airway surfaces of smokers is not well defined. To address these issues, concentrations of nicotine, cotinine, and hydroxycotinine were measured by mass spectrometry (MS) in supernatants of induced sputum obtained from participants in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS), an ongoing observational study that included never smokers, former smokers, and current smokers with and without chronic obstructive pulmonary disease (COPD).

The Portfolio Diet and Incident Type 2 Diabetes: Findings From the Women's Health Initiative Prospective Cohort Study.

Objective: A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes.

Research Design And Methods: This analysis included 145,299 postmenopausal women free of diabetes at baseline in the Women's Health Initiative (WHI) Clinical Trials and Observational Study from 1993 to 2021.

Development of a Portfolio Diet Score and Its Concurrent and Predictive Validity Assessed by a Food Frequency Questionnaire.

The Portfolio Diet, a plant-based portfolio of cholesterol-lowering foods, has been shown to reduce low-density lipoprotein cholesterol (LDL-C), and other cardiovascular risk factors, in randomized controlled trials (RCTs). It is not known if these beneficial effects translate to a lower incidence cardiovascular disease (CVD) risk. To support examinations between Portfolio Diet adherence and disease, a Portfolio Diet score (PDS) was developed and its predictive and concurrent validity was assessed within the Toronto Healthy Diet Study, a six-month RCT in overweight adults.

Relationship Between a Plant-Based Dietary Portfolio and Risk of Cardiovascular Disease: Findings From the Women's Health Initiative Prospective Cohort Study.

Background The plant-based Dietary Portfolio combines established cholesterol-lowering foods (plant protein, nuts, viscous fiber, and phytosterols), plus monounsaturated fat, and has been shown to improve low-density lipoprotein cholesterol and other cardiovascular disease (CVD) risk factors. No studies have evaluated the relation of the Dietary Portfolio with incident CVD events. Methods and Results We followed 123 330 postmenopausal women initially free of CVD in the Women's Health Initiative from 1993 through 2017.

Metabolism of Anethole Dithiolethione by Rat and Human Liver Microsomes: Formation of Various Products Deriving from Its -Demethylation and -Oxidation. Involvement of Cytochromes P450 and Flavin Monooxygenases in These Pathways.

A study of the metabolism of anethole dithiolethione (ADT, 5-(p-methoxyphenyl)-3-1,2-dithiole-3-thione) by rat and human liver microsomes showed the formation of the corresponding -oxide and the -oxide of desmethyl-ADT (dmADT, 5-(p-hydroxyphenyl)-3-1,2-dithiole-3-thione), and of p-methoxy-acetophenone (pMA) and p-hydroxy-acetophenone (pHA), in addition to the previously described metabolites, dmADT, anethole dithiolone (ADO, 5-(p-methoxyphenyl)-3-1,2-dithiole-3-one) and its demethylated derivative dmADO [5-(p-hydroxyphenyl)-3-1,2-dithiole-3-one]. The microsomal metabolism of ADO under identical conditions led to dmADO and to pMA and pHA. The metabolites of ADT derive from two competing oxidative pathways: an -demethylation catalyzed by cytochromes P450 and an -oxidation mainly catalyzed by flavin-dependent monooxygenases (FMO) and, to a minor extent, by CYP enzymes.

Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients.

Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)].

Randomized trial of TAS-102 for refractory metastatic colorectal cancer.

Background: Early clinical trials conducted primarily in Japan have shown that TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride, was effective in the treatment of refractory colorectal cancer. We conducted a phase 3 trial to further assess the efficacy and safety of TAS-102 in a global population of such patients.

Methods: In this double-blind study, we randomly assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo.

N-Hydroxyguanidines oxidation by a N3S copper-complex mimicking the reactivity of Dopamine beta-Hydroxylase.

N-Aryl-N'-hydroxyguanidines are compounds that display interesting pharmacological properties but their chemical reactivity remains poorly investigated. Some of these compounds are substrates for the heme-containing enzymes nitric-oxide synthases (NOS) and act as reducing co-substrates for the copper-containing enzyme Dopamine beta-Hydroxylase (DBH) [P. Slama, J.

Disordered connectivity in the autistic brain: challenges for the "new psychophysiology".

In 2002, we published a paper [Brock, J., Brown, C., Boucher, J.