- Carcinogens and Genotoxicity Assessment
- Indoor Air Quality and Microbial Exposure
- Autoimmune and Inflammatory Disorders Research
- Air Quality and Health Impacts
- Inhalation and Respiratory Drug Delivery
- Hypothalamic control of reproductive hormones
- Kawasaki Disease and Coronary Complications
- Pregnancy-related medical research
- Smoking Behavior and Cessation
- Adolescent and Pediatric Healthcare
- Animal testing and alternatives
- Signaling Pathways in Disease
- Reproductive System and Pregnancy
- Cytokine Signaling Pathways and Interactions
- Growth Hormone and Insulin-like Growth Factors
- Molecular Biology Techniques and Applications
- Endometriosis Research and Treatment
- Ion channel regulation and function
- Pregnancy and preeclampsia studies
- Skin Protection and Aging
- Preterm Birth and Chorioamnionitis
- Neurogenetic and Muscular Disorders Research
- Dental Trauma and Treatments
- Dental Erosion and Treatment
- Radiation Effects and Dosimetry
British American Tobacco (United Kingdom)
2013-2022
National Hospital for Neurology and Neurosurgery
2007
University College London
2007
Guy's Hospital
2007
King's College London
2007
Proteome Sciences (United Kingdom)
2007
St Thomas' Hospital
2002-2004
Medical Research Council
2000
MRC Centre for Reproductive Health
2000
Huntington's disease (HD) causes widespread CNS changes and systemic abnormalities including endocrine immune dysfunction. HD biomarkers are needed to power clinical trials of potential treatments. We used multiplatform proteomic profiling reveal plasma with progression. Proteins interest were evaluated using immunoblotting ELISA in from 2 populations, CSF R6/2 mice. The identified proteins demonstrate neuroinflammation warrant further investigation as possible biomarkers. Keywords: •...
We have previously reported increased protein expression of sarcoplasmic reticulum calcium ATPase (SERCA) 2b in myometrium from women labor at term, but the stimulus for this change is unknown. Proinflammatory cytokines been implicated cascade events leading to preterm and term labor, we hypothesize that interleukin (IL)-1β may induce changes key homeostatic mechanisms and, turn, augment myometrial contractility before labor. The aim present study was investigate long-term effects IL-1β on...
The mechanisms underlying the switch from uterine quiescence to contractile activity in labour are not clearly understood. Increasing evidence suggests that pathways of myometrial calcium homeostasis, including store-operated entry (SOCE), may play an important role. molecular basis membrane-associated channels contributing SOCE pregnant human myometrium is known, but they likely be hetero- or homo-oligomeric assemblies transient receptor potential channel (TrpC) proteins, encoded by...
Stretch is known to stimulate myometrial hyperplasia and hypertrophy in early pregnancy uterine contraction at term.We propose that transduction of the stretch signal involves alteration intracellular calcium signalling, including changes transient receptor potential canonical (TRPC) isoform expression.The aim present study was investigate effect prolonged mechanical (tonic) vitro on human smooth muscle cell signalling TRPC expression.Cells were cultured from biopsies, obtained women...
The development of whole smoke exposure systems have been driven by the fact that traditional techniques are based on particulate phase tobacco and not complete aerosol. To overcome these challenges in this study, we used a Vitrocell® VC 10 system. For characterisation purposes, determined deposition relationship to airflow (L/min), regional within linear module, vapour dilution using known marker (carbon monoxide) finally assessed biological responses two independent systems, Ames Neutral...
There are several whole smoke exposure systems used to assess the biological and toxicological impact of tobacco in vitro. One such system is Vitrocell® VC 10 Smoking Robot module. Using quartz crystal microbalances (QCMs) installed into module, we were able particle deposition real-time. We compared regional across module positions doses delivered by six 10s four independent laboratories: two UK, one Germany China. Gauge R&r analysis was applied total data package from 10s. As a percentage...
Cigarette smoking is a cause of variety serious diseases, and to understand the toxicological impact tobacco smoke in vitro, whole exposure systems can be used. One main challenges different that are commercially available they dilute deliver ways, limiting/restricting cross-comparison biological responses. This where dosimetry – dose quantification play key role data comparison. Quartz crystal microbalance (QCM) technology has been put forward as one such tool quantify particle deposition...
Salmonella typhimurium strains TA1535, TA1537, TA97, TA102 and TA104 were assessed for their suitability use in conjunction with a Vitrocell(®) VC 10 Smoking Robot 3R4F reference mainstream cigarette smoke. Little information exists on TA104, TA1537 using an aerosol 35mm spread-plate format. In this study, TA1535 considered sub-optimal scaled-down format, due to low spontaneous revertant numbers (0-5 revertants/plate). the context of regulatory environment, TA97 is deemed acceptable...
Abstract This study investigated gestational regulation of transient receptor potential canonical (TrpC) proteins, putative calcium entry channels in human myometrium, and the modulation TrpC expression by IL–1β, a cytokine implicated labor. Total RNA proteins were isolated from myometrial biopsies obtained NP women, pregnant women at term not labor (TNL), or active (TAL) primary cultured smooth muscle cells incubated with IL–1β without nimesulide. Semiquantitative RT-PCR demonstrated...
To date there are no widely accepted methods for the toxicological testing of complex gaseous mixtures and aerosols, such as cigarette smoke, although some modifications to standard regulatory have been developed used. Historically, routine cigarettes has primarily focused on particulate fraction smoke. However, this may not accurately reflect full toxicity mutagenicity smoke aerosol a whole, which contains semi-volatiles short-lived products combustion. In study we used modified version...
Tobacco smoke toxicity has traditionally been assessed using the particulate fraction under submerged culture conditions which omits vapour phase elements from any subsequent analysis. Therefore, methodologies that assess full interactions and complexities of tobacco are required. Here we describe adaption a modified BALB/c 3T3 neutral red uptake (NRU) cytotoxicity test methodology, is based on Interagency Coordinating Committee Validation Alternative Methods (ICCVAM) protocol for in vitro...
This study describes the evaluation of a modified air-liquid interface BALB/c 3T3 cytotoxicity method for assessment smoke aerosols in vitro. The functionality and applicability this protocol was assessed by comparing profiles from eight different cigarettes. Three reference cigarettes, 1R5F, 3R4F CORESTA Monitor 7 were used to put data into perspective five bespoke experimental products manufactured, ensuring balanced controlled study. Manufactured cigarettes matched key variables such as...
There is a growing consensus that e-cigarettes hold the potential for reducing harm associated with cigarette smoking. Recently published studies have reported in vitro testing of e-cigarettes, demonstrating reduced toxicological and biological effects. Few however use under extreme conditions. To assess full mutagenic commercially available electronic-cigarette (Vype ePen), this study investigated delivery aerosol conditions, using scaled-down 35 mm plate Ames bacterial reverse mutagenicity...
Smoking is a cause of serious diseases, including lung cancer, emphysema, chronic bronchitis and heart disease. DNA damage thought to be one the mechanisms by which cigarette smoke (CS) initiates disease in lung. Indeed, CS induced can measured vitro vivo. The potential Comet assay measure isolated rat alveolar type II epithelial cells (AEC II) was explored as means include genotoxicity end-point rodent sub-chronic inhalation studies. In this study, published AEC isolation methods were...
Abstract Background The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) to compare initiation strategies for systemic juvenile idiopathic arthritis (sJIA). First-line options sJIA (FROST) was a prospective observational study assess CTP outcomes using the CARRA Registry. Methods Patients with new-onset were enrolled if they received initial according biologic CTPs (IL-1 or IL-6 inhibitor) non-biologic (glucocorticoid (GC) monotherapy...
Tobacco smoke from a combustible cigarette contains more than 6000 constituents; approximately 150 of these are identified as toxicants. Technologies that modify the tobacco blend to reduce toxicant emissions have been developed. These include sheet substitute dilute toxicants in and treated levels nitrogenous precursors some polyphenols. Filter additives gas (vapour) phase constituents also In this study, both filter technologies were combined into an experimental smoked International...
Many laboratories are working to develop in vitro models that will replace vivo tests, but occasionally there remains a regulatory expectation of some testing. Historically, cigarettes have been tested for 90 days. Recently, methods reduce and refine animal use explored. This study investigated the potential reducing cigarette smoke (CS) exposure 3 or 6 weeks, feasibility separate lung lobes histopathology Comet assay. Rats were exposed sham air CS (1 2 h) weeks. Respiratory tissues...
Abstract Background Long‐term use of cigarettes can result in localised staining and aging smokers’ skin. The tobacco heating products (THPs) electronic (ECs) has grown on a global scale; however, the long‐term effect these products’ aerosols consumers’ skin is unknown. This pilot clinical study aimed to determine whether THP or EC aerosol exposure results activation biomarkers associated with oxidative stress. Materials methods Eight areas were identified backs 10 subjects. Two used for air...
To report baseline characteristics, patient reported outcomes and treatment of children with Juvenile Dermatomyositis (JDM) in the Childhood Arthritis Rheumatology Research Alliance (CARRA) Registry.Children newly diagnosed JDM were enrolled CARRA Registry from 41 pediatric rheumatology centers. Baseline demographics, disease assessments, outcome treatments recorded.In first year, 119 participants enrolled. Most female (63.4%), white (72.3%) a median diagnosis age 8.0 years (IQR 4.0-11.5),...
The impact of social determinants health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation treatment for pJIA important to prevent disease morbidity; however, a potential barrier early pJIAs delayed presentation pediatric rheumatologist. We examined the community poverty level, key determinant health, time from patient reported symptom onset first rheumatology visit among patients enrolled in Childhood Arthritis and Rheumatology...
This work investigates a completely novel and experimental concept of exposing L5178Y cells at the air-agar-interface to mainstream cigarette smoke aerosol (Kentucky reference 3R4F). study highlights associated challenges combining suspension cell line alongside an in vitro exposure system. To achieve monolayer, were 'seeded' concentrated super-mix onto RPMI/agar-matrix -base. The resulting media was adsorbed into agar base leaving lightly suspended on surface, approximating monolayer. Cells...
Tobacco smoke (CS) may visually stain indoor surfaces including ceilings, walls and soft furnishings over time. Potentially reduced risk products (PRRPs) such as e-cigarettes (EC) tobacco heating (THP) produce chemically less complex aerosols with significantly levels of toxicants, particles odour. However, the potential effects EC THP on staining are currently unknown. In this study, an exposure chamber was developed a model system to enable accelerated wallpaper cotton samples by...