Development of a method to assess cigarette smoke intake

Tar and nicotine deliveries of cigarettes measured using current standardized smoking machine protocols provide poor estimates of smoke exposure. The characteristics of human smoking behavior vary considerably and differ from the rigid parameters used with current standardized smoking machine protocols. Current alternatives, including measurement of biomarkers, are invasive, time-dependent, and can be too expensive to be used as mechanisms for carrying out large-scale investigations required to help determine the influence of cigarette design on smoking behaviors. To obtain more reasonable estimates of mainstream smoke exposure, we developed a method to quantitatively measure solanesol, a naturally occurring component in tobacco that is deposited during smoking in the cigarette filter butt. Quantification of solanesol extracted from the filters using liquid chromatography and tandem mass spectrometry is efficient, rapid, and extremely reliable. We found that the amount of solanesol deposited in a cigarette filter is related to the mainstream smoke deliveries of tar and nicotine under a variety of smoking conditions. In addition, the amount of solanesol trapped in the filter remains stable at least 4 weeks after smoking. Measuring solanesol in cigarette filters as an exposure marker provides a noninvasive means to obtain reasonable estimates of mainstream tar and nicotine smoke deliveries under a wide variety of smoking conditions.     

State legislators' perceptions of lobbyists and lobbying on tobacco control issues

OBJECTIVE: To determine state legislators' perceptions about health and tobacco lobbyists, their frequency of contact with these lobbyists, and the amount of campaign contributions from health professional organisations and the tobacco industry. DESIGN: Cross-sectional study. SUBJECTS: State legislators from North Carolina, Texas, and Vermont (USA), serving in 1994. MAIN OUTCOME MEASURES: Perceptions about lobbyists representing the tobacco industry, non-profit health organisations, and state medical societies with respect to their credibility, importance as sources of information, and persuasiveness; extent of lobbying activities; campaign contributions from health professional organisations and the tobacco industry. RESULTS: Almost all legislators reported that medical society and non-profit health organisation lobbyists are credible on tobacco issues and just over half believed that these lobbyists are important sources of information. More legislators said they could be persuaded by medical and health lobbyists than by tobacco lobbyists. Although health professional Political Action Committees (PACs) gave campaign contributions to more state legislators, and gave higher amounts on average, than tobacco PACs, legislators reported less contact with medical society lobbyists than tobacco lobbyists about tobacco issues. CONCLUSIONS: State legislators have positive attitudes toward lobbyists for non-profit health organisations and state medical societies regarding tobacco issues. These groups may be an underused resource for educating legislators about tobacco control measures.


     

CNTs in Optoelectronic Devices: New Structural and Photophysical Insights on Porphyrin‐DWCNTs Hybrid Materials

The preparation and physical characterization of diverse porphyrin‐derived double‐walled carbon nanotubes (DWCNTs) conjugates are described. A porphyrin molecule is covalently linked and physically adsorbed to COOH‐derived DWCNTs. The photophysical properties of all porphyrin‐CNTs derivatives are studied in solution and in polymeric matrices. Definitive experimental evidence for photoinduced electron and/or energy transfer processes involving the porphyrin chromophores and the CNT wall is not obtained, but solid‐state UV‐vis absorption profiles display electronic transitions fingerprinting J‐ and H‐ type aggregates, where porphyrin molecules intermolecularly interact “head‐to‐tail” and “face‐to‐face”, respectively. In parallel, molecular modeling based on force‐field simulations is performed to understand the structure of the porphyrin‐CNTs interface and the nature of the interactions between the porphyrins and the DWCNTs. Finally, multilayered ‐ type devices are fabricated with the aim of investigating the interaction of the porphyrin‐derived DWCNTs with poly(3‐hexylthiophene)‐pyrene matrices containing small amounts of 1‐[3‐(methoxycarbonyl)propyl]‐1‐phenyl‐[6.6]C₆₁.     

Improved rapid authentication of vanillin using δ13C and δ2H values

Vanilla still remains one of the most important and widely used flavours in the food industry and is also extensively employed by fragrance and pharmaceutical manufacturing companies. Natural vanilla flavour, extracted from the pods of the tropic orchid vanilla, is considerably more expensive than synthetic vanillin. The disparity of prices between natural vanillin and that derived from other sources has given rise to many cases of fraudulent adulteration, and for more than 30 years, strenuous efforts have been made to authenticate sources of vanillin. Stable isotope analysis is one of the most powerful analytical tools to distinguish between natural vanillin and that originating from other sources. Recently, a rapid and precise method for analysis of both δ¹³C and δ²H values of plant methoxyl groups has been published. Here, we report an application of the method for the control of authenticity of vanillin. Carbon and hydrogen stable isotope values of the vanillin molecule and vanillin methoxyl groups of vanillin samples of different origins including authentic and synthetic samples were measured. The results clearly show that use of this approach provides a rapid and reliable authenticity assessment of vanillin. The technique used for these studies is robust and rapid, involves minimum sample preparation and requires only a small amount of vanillin sample, usually 1 mg for stable carbon and 4 mg for stable hydrogen analysis.     

Wavefront-based models for inverse electrocardiography

We introduce two wavefront-based methods for the inverse problem of electrocardiography, which we term wavefront-based curve reconstruction (WBCR) and wavefront-based potential reconstruction (WBPR). In the WBCR approach, the epicardial activation wavefront is modeled as a curve evolving on the heart surface, with the evolution governed by factors derived phenomenologically from prior measured data. The body surface potential/wavefront relationship is modeled via an intermediate mapping of wavefront to epicardial potentials, again derived phenomenologically. In the WBPR approach, we iteratively construct an estimate of epicardial potentials from an estimated wavefront curve according to a simplified model and use it as an initial solution in a Tikhonov regularization scheme. Initial simulation results using measured canine epicardial data show considerable improvement in reconstructing activation wavefronts and epicardial potentials with respect to standard Tikhonov solutions. In particular the WBCR method accurately finds the anisotropic propagation early after epicardial pacing, and the WBPR method finds the wavefront (regions of sharp gradient of the potential) both accurately and with minimal smoothing.     

Inhibition of Human Urokinase-Type Plasminogen Activator (uPA) Enzyme Activity and Receptor Binding by DNA Aptamers as Potential Therapeutics through Binding to the Different Forms of uPA

Urokinase-type plasminogen activator is widely discussed as a marker for cancer prognosis and diagnosis and as a target for cancer therapies. Together with its receptor, uPA plays an important role in tumorigenesis, tumor progression and metastasis. In the present study, systematic evolution of ligands by exponential enrichment (SELEX) was used to select single-stranded DNA aptamers targeting different forms of human uPA. Selected aptamers allowed the distinction between HMW-uPA and LMW-uPA, and therefore, presumably, have different binding regions. Here, uPAapt-02-FR showed highly affine binding with a K_D of 0.7 nM for HMW-uPA and 21 nM for LMW-uPA and was also able to bind to pro-uPA with a K_D of 14 nM. Furthermore, no cross-reactivity to mouse uPA or tissue-type plasminogen activator (tPA) was measured, demonstrating high specificity. Suppression of the catalytic activity of uPA and inhibition of uPAR-binding could be demonstrated through binding with different aptamers and several of their truncated variants. Since RNA aptamers are already known to inhibit uPA-uPAR binding and other pathological functions of the uPA system, these aptamers represent a novel, promising tool not only for detection of uPA but also for interfering with the pathological functions of the uPA system by additionally inhibiting uPA activity.     

No Time to Die: How Kidney Cancer Evades Cell Death

The understanding of the pathogenesis of renal cell carcinoma led to the development of targeted therapies, which dramatically changed the overall survival rate. Nonetheless, despite innovative lines of therapy accessible to patients, the prognosis remains severe in most cases. Kidney cancer rarely shows mutations in the genes coding for proteins involved in programmed cell death, including p53. In this paper, we show that the molecular machinery responsible for different forms of cell death, such as apoptosis, ferroptosis, pyroptosis, and necroptosis, which are somehow impaired in kidney cancer to allow cancer cell growth and development, was reactivated by targeted pharmacological intervention. The aim of the present review was to summarize the modality of programmed cell death in the pathogenesis of renal cell carcinoma, showing in vitro and in vivo evidence of their potential role in controlling kidney cancer growth, and highlighting their possible therapeutic value.     

Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis

Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on the anti-inflammatory, anti-oxidant and analgesic effects of cannabidiol (CBD) and on its potential role in endometriosis. We employed an in vivo model of endometriosis and administered CBD daily by gavage. CBD administration strongly reduced lesions diameter, volume and area. In particular, it was able to modify lesion morphology, reducing epithelial glands and stroma. CBD showed anti-oxidant effects reducing lipid peroxidation, the expression of Nox-1 and Nox-4 enzymes. CBD restored the oxidative equilibrium of the endogenous cellular defense as showed by the SOD activity and the GSH levels in the lesions. CBD also showed important antifibrotic effects as showed by the Masson trichrome staining and by downregulated expression of MMP-9, iNOS and TGF-β. CBD was able to reduce inflammation both in the harvested lesions, as showed by the increased Ikb-α and reduced COX2 cytosolic expressions and reduced NFkB nuclear localization, and in the peritoneal fluids as showed by the decreased TNF-α, PGE2 and IL-1α levels. CBD has important analgesic effects as showed by the reduced mast cells recruitment in the spinal cord and the reduced release of neuro-sensitizing and pro-inflammatory mediators. In conclusion, the collected data showed that CBD has an effective and coordinated effects in endometriosis suppression.