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2.
Appetite ; 142: 104375, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31326437

ABSTRACT

Little is known whether small modifications of food texture are sufficient to influence satiation. This study used four iso-caloric yogurts differing in viscosity (low/high) and granola particle size (small/large) to investigate the influence of small texture modifications on oral processing behaviour, eating rate and ad libitum intake. Yogurt viscosity differed by a factor of 1.57x to 1.81x. Granola particle size was 6 mm and 12 mm (2-fold difference). Granola particle concentration based on weight was constant (15% w/w). Oral processing behaviour was quantified by video recording consumers eating yogurt ad libitum (n = 104). Ratings for appetite, liking and product familiarity were also quantified. A decrease in yogurt viscosity significantly decreased spoon size, number of chews per spoon and oral exposure time per spoon but did not significantly affect eating rate and ad libitum intake. A decrease in granola particle size from 12 mm to 6 mm at constant weight concentration significantly increased number of chews per spoon and decreased spoon size, eating rate and ad libitum intake without affecting liking. The differences in eating rate and ad libitum intake between yogurts containing small and large granola particles were 5 g/min (7%) and 17 g (5%), respectively. We suggest that the volume of granola particles added to the yogurt and not the size of particles per se was the driver of oral processing behaviour. We conclude that relatively small modifications in yogurt texture, especially granola particle size, are sufficient to change oral processing behaviour and ad libitum intake. These findings demonstrate that small texture modifications of foods, such as the size of granola particles added to yogurt, can be used to modulate eating rate and food intake within a meal.


Subject(s)
Eating/psychology , Edible Grain/chemistry , Feeding Behavior/psychology , Satiation , Yogurt/analysis , Adolescent , Adult , Female , Humans , Male , Netherlands , Particle Size , Viscosity , Young Adult
3.
Food Res Int ; 115: 292-301, 2019 01.
Article in English | MEDLINE | ID: mdl-30599944

ABSTRACT

The aim of the present research was to explore consumers' conceptualization of feeling good in relation to food and beverages from a cross-cultural perspective. Participants from 14 countries across 5 continents and covering 10 languages (N = 8325) responded to an online survey including word association and free listing tasks related to feeling good in the context of food and beverages. Results were analyzed using inductive coding: a list of main codes was generated in English for each of the tasks, after which native speakers for each language coded the responses. Codes were grouped into categories reflecting common themes from which eight dimensions were identified. Results showed that in the context of foods and beverages, feeling good was mainly associated with specific foods and sensory and hedonic properties. Across the 14 countries, 'Sweet and fat food', 'Fruit and vegetables', and 'Protein food' were the three food categories most associated with feeling good. Emotional aspects of food consumption ('Taste good' and emotions) were also relevant. Health and nutrition-related aspects were more relevant for consumers when they were asked to think about how foods and beverages would make them feel good in the future. In other words, food-related feeling good seems to be mainly driven by sensory pleasure at present, but it is also related to nutrition and health in the future. Differences in the strength of the associations between feeling good and the identified categories were found between countries, in line with the existence of cultural differences in food habits, as well as in the importance people attach to the characteristics of foods and beverages. Results from the present work provide insights on the impact of eating and drinking on feeling good in terms of emotional, physical and social aspects, and increase knowledge about the way food and drink can contribute to general well-being.


Subject(s)
Beverages , Cross-Cultural Comparison , Emotions , Food Preferences , Adolescent , Adult , Aged , Eating , Feeding Behavior , Fruit , Humans , Middle Aged , Surveys and Questionnaires , Taste , Vegetables , Young Adult
4.
J Psychosom Res ; 68(2): 109-16, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20105692

ABSTRACT

OBJECTIVE: Evidence suggests that emotional stress can trigger acute coronary syndromes in patients with advanced coronary artery disease (CAD), although the mechanisms involved remain unclear. Hostility is associated with heightened reactivity to stress in healthy individuals, and with an elevated risk of adverse cardiac events in CAD patients. This study set out to test whether hostile individuals with advanced CAD were also more stress responsive. METHODS: Thirty-four men (aged 55.9+/-9.3 years) who had recently survived an acute coronary syndrome took part in laboratory testing. Trait hostility was assessed by the Cook Medley Hostility Scale, and cardiovascular activity, salivary cortisol, and plasma concentrations of interleukin-6 were assessed at baseline, during performance of two mental tasks, and during a 2-h recovery. RESULTS: Participants with higher hostility scores had heightened systolic and diastolic blood pressure (BP) reactivity to tasks (both P<.05), as well as a more sustained increase in systolic BP at 2 h post-task (P=.024), independent of age, BMI, smoking status, medication, and baseline BP. Hostility was also associated with elevated plasma interleukin-6 (IL-6) levels at 75 min (P=.023) and 2 h (P=.016) poststress and was negatively correlated with salivary cortisol at 75 min (P=.034). CONCLUSION: Hostile individuals with advanced cardiovascular disease may be particularly susceptible to stress-induced increases in sympathetic activity and inflammation. These mechanisms may contribute to an elevated risk of emotionally triggered cardiac events in such patients.


Subject(s)
Acute Coronary Syndrome/psychology , Hostility , Stress, Psychological/physiopathology , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/physiopathology , Analysis of Variance , Anxiety/blood , Anxiety/physiopathology , Anxiety/psychology , Blood Pressure/physiology , Depression/blood , Depression/physiopathology , Depression/psychology , Enzyme-Linked Immunosorbent Assay , Humans , Hydrocortisone/analysis , Interleukin-6/blood , Luminescence , Male , Middle Aged , Neuropsychological Tests , Personality Inventory , Regression Analysis , Saliva/chemistry , Stress, Psychological/blood , Stress, Psychological/psychology , Surveys and Questionnaires , Sympathetic Nervous System/physiopathology , Time Factors
5.
Integr Biol (Camb) ; 1(3): 260-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-20023737

ABSTRACT

Bio-electrospraying, a recently discovered, direct electric field driven cell engineering process, has been demonstrated to have no harmful effects on treated cells at a molecular level. Although several cell types from both immortalized and primary cultures have been assessed post-treatment as a function of time in comparison to controls, the protocol has yet to be applied on embryonic stem cells. This is most important if bio-electrosprays are to further their applicability, in particular with regard to tissue engineering and regenerative medicine, where embryonic stem cells play a fundamental role. In the study presented herein the chosen stem cells are mouse embryonic stem (ES) cells. Hence, these first examples where embryonic stem cells have been jetted by way of bio-electrosprays, demonstrate the cellular viability and the cell's pluripotency indistinguishable when comparing those post-treated cells with their respective controls.


Subject(s)
Embryonic Stem Cells/cytology , Embryonic Stem Cells/physiology , Micro-Electrical-Mechanical Systems/methods , Micromanipulation/methods , Specimen Handling/methods , Tissue Engineering/methods , Animals , Cell Differentiation , Cell Survival , Humans
6.
Eur J Nucl Med Mol Imaging ; 36(12): 2027-33, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19618180

ABSTRACT

PURPOSE: Despite modern CT systems and expert evaluators, the diagnostic performance of coronary CT angiography is limited by overestimation of vessel stenosis which reduces the positive predictive value (PPV) of the test. The aim of this study was to evaluate the performance of combined cardiac PET/64-detector CT angiography. METHODS: Included in this retrospective study were 33 consecutive patients (5 women, 28 men; mean age 61.6 years, range 47-87 years, mean BMI 27.3+/-5.2 kg/m(2)) with clinically suspected flow-limiting coronary artery disease who underwent combined cardiac PET/64-detector CT angiography and invasive angiography. Combined PET/CT images were reported by an experienced dual-accredited radiologist/nuclear physician. An experienced cardiac CT radiologist re-read the CT images without PET. Stenotic disease was defined as >50% vessel narrowing. Invasive coronary angiography was used as a reference standard. Local ethics committee approval and patient consent were obtained. RESULTS: CT angiography (without PET data) was concordant with invasive angiography in 31/33 patients and at a patient level, the sensitivity in detecting significant coronary artery lesions was 100%, the specificity was 82%, the PPV was 92% and the negative predictive value (NPV) was 100%. Using combined PET/CT angiography the findings were concordant with invasive angiography in 32/33 patients and at a patient level, the sensitivity was 96%, the specificity was 100%, the PPV was 100% and the NPV was 91%. CONCLUSION: The use of integrated cardiac PET/64-detector CT angiography is feasible and appears to improve some aspects of the diagnostic performance of 64-detector coronary artery angiography in detecting coronary artery disease.


Subject(s)
Coronary Angiography/methods , Heart/diagnostic imaging , Positron-Emission Tomography/methods , Systems Integration , Tomography, X-Ray Computed/methods , Aged , Coronary Angiography/standards , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/physiopathology , Female , Heart/physiopathology , Humans , Male , Middle Aged , Myocardial Perfusion Imaging , Observer Variation , Reference Standards , Retrospective Studies , Stroke Volume
8.
Clin Med (Lond) ; 9(6): 560-2, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20095299

ABSTRACT

This one-day conference brought together around 100 doctors from a wide range of specialties and at different stages of their careers to examine areas that are of increasing importance to the profession as a whole. Information gathered and imparted to institutions such as the postgraduate deaneries, royal colleges and specialist societies will add to the impetus for cultural and organisational changes so that the real potential of doctors working less than full time is not lost to the economy, NHS or patients.


Subject(s)
Practice Patterns, Physicians'/standards , Work Schedule Tolerance , Workload/statistics & numerical data , Congresses as Topic , Humans , United Kingdom
9.
Biomed Mater ; 3(2): 025008, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18458371

ABSTRACT

This paper reports developments on a hybrid cell-engineering protocol coupling both bio-electrosprays and aerodynamically assisted bio-jets for process-handling living cells. The current work demonstrates the ability to couple these two cell-jetting protocols for handling a wide range of cells for deposition. The post-treated cells are assessed for their viability by way of flow cytometry, which illustrates a significant population of viable cells post-treatment in comparison to those controls. This work is the first example of coupling these two protocols for the process handling of living cells. The hybrid protocol demonstrates the achievement of stable cone jetting of a cellular suspension in the single-needle configuration which was previously unachieved with single-needle bio-electrosprays. Furthermore the living cells explored in these investigations expressed GFP, thus demonstrating the ability to couple gene therapy with this hybrid protocol. Hence, this approach could one day be explored for building biologically viable tissues incorporating a therapeutic payload for combating a range of cellular/tissue-based pathologies.


Subject(s)
Cell Culture Techniques/methods , Cell Separation/methods , Kidney/cytology , Kidney/physiology , Microfluidics/methods , Micromanipulation/methods , Tissue Engineering/methods , Cell Line , Humans , Injections, Jet , Pressure
10.
Mol Ther ; 16(3): 508-15, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18180778

ABSTRACT

We have developed new, synthetic vector formulations that display high efficiency of gene transfer to vascular cells and tissues. The formulations comprise cationic liposomes and cationic, receptor-targeting peptides that self assemble on mixing with plasmid DNA into receptor-targeted nanocomplexes (RTNs). One such RTN formulation was optimal for transfection of primary smooth muscle cells (LYD-1), while a second was optimal for transfection of rabbit aortic explants (LYD-2). In both RTNs, the peptide was a 16-lysine motif linked to the targeting sequence CYGLPHKFCG via a short spacer sequence. The major difference between LYD-1 and LYD-2 lay in the cationic lipid component, where LYD-1 contained ditetradecyl trimethyl ammonium (DTDTMA), an unsaturated, cationic lipid with a 14-carbon alkyl tail, whereas LYD-2 contained 2,3-dioleyloxypropyl-1-trimethyl ammonium chloride (DOTMA), a cationic lipid with an 18-carbon unsaturated alkyl tail. LYD-2 transfections of aortic explants were effective with incubations performed at room temperature for as little as 30 minutes, with either saline or glucose-based solutions. Transgene expression in the explants peaked at 5 days and persisted for 14 days. The kinetics of transfected gene expression, along with the efficacy of transfection with short incubation times, indicate that these new formulations may be useful tools in the development of molecular therapies for cardiovascular diseases.


Subject(s)
Aorta/cytology , Muscle, Smooth, Vascular/metabolism , Nanoparticles/chemistry , Receptors, Cell Surface/genetics , Animals , Cells, Cultured , Gene Transfer Techniques , Genetic Vectors/genetics , Humans , Kinetics , Liposomes/chemistry , Male , Muscle, Smooth, Vascular/cytology , Organ Culture Techniques , Peptides/chemistry , Plasmids/chemistry , Plasmids/genetics , Polymerase Chain Reaction , Rabbits , Swine , Transfection/methods
11.
Soft Matter ; 4(6): 1219-1229, 2008 May 14.
Article in English | MEDLINE | ID: mdl-32907265

ABSTRACT

Electrosprays and electrospinning were recently pioneered for directly handling living cells. These recent discoveries are now widely referred to as "bio-electrosprays" and "cell electrospinning", which have been demonstrated as having tremendous applicability to the life sciences in regenerative and therapeutic medicine. In the current work, we report our developmental studies with these protocols as submerged entities with primary rabbit aorta smooth muscle cells for generating cell-bearing encapsulations, which demonstrate proof-of-concept for a plethora of biomedical applications. Cell viability of the post-treated cells was assessed in comparison with two controls by way of flow cytometry over a three week period, establishing a viable cellular population >70%. Hence these investigations demonstrate the ability to explore these electrified encapsulating approaches for directly forming biologically viable emulsions, which could potentially be exploited from mechanisms for cancer therapy, hormone, and diabetic treatment to applications with cosmetics. Therefore, these studies elucidate the strong implications these bio-protocols have to offer the life sciences.

12.
Biotechnol J ; 3(1): 124-8, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17722180

ABSTRACT

Recent interests in the fabrication of bio/cell-friendly surfaces are consistently gaining much scientific coverage as these methods could be explored as novel regenerative and therapeutic medicinal protocols. Essentially two main components govern this aspect, the processing methodology possessing the required robustness to fabricate a wide range of materials and, not least, the synthesised materials that need to be cell-compatible both in the short and long term after processing. In the study reported here we have combined one such robust jetting approach with a specially formulated siloxane sol. This has several unique properties in itself, and these have been demonstrated here to have a positive effect on the seeded cells. The current work demonstrates that this approach has great promise as a novel methodology for surface engineering for a wide range of applications spanning the physical to the life science areas of research.


Subject(s)
Biocompatible Materials/chemistry , Cell Culture Techniques/instrumentation , Cell Culture Techniques/methods , Chemistry, Physical/methods , Tissue Engineering/instrumentation , Tissue Engineering/methods , Materials Testing , Surface Properties
13.
Eur J Nucl Med Mol Imaging ; 34(12): 1965-72, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17768620

ABSTRACT

PURPOSE: Myocardial perfusion with PET/CT has advantages over conventional SPECT. We describe our initial European experience using (82)Rubidium-PET/CT, as part of a clinical myocardial perfusion service. METHODS: We studied the first 100 patients (64 male; 36 female, mean age = 60: SD +/-12.5y, mean body mass index = 30: SD +/-6.9kg/m( 2 )) who underwent (82)Rubidium cardiac PET/CT in our institution. Thirty patients had recently undergone coronary angiography. Patients underwent imaging during adenosine infusion and at rest. Images were acquired over 5 minutes using a GE-PET/CT instrument. Image quality was described as good, adequate or inadequate. Images were reported patient-by-patient by a minimum of five nuclear medicine physicians. A segment-by-segment analysis (17-segment model) was also performed. RESULTS: Image quality was good in 77%, adequate 23% and inadequate 0%. There was no statistical difference in image quality between obese and non-obese patients (Fisher's exact test, p = 0.2864). 59% had normal perfusion studies, 29% had inducible ischaemia, 12% had myocardial infarction (11% with super added ischaemia). There was reduced (82)Rubidium uptake in 132/1700 segments during stress. There was reduced (82)Rubidium uptake at rest in 42/1700 segments. The (82)Rubidium PET/CT findings were consistent with the angiographic findings in 28/30 cases. CONCLUSION: We show that, even from initial use of (82)Rubidium, it is possible to perform myocardial perfusion studies quickly with good image quality, even in the obese. The PET findings correlated well in the third of the cases where angiography was available. As such, (82)Rubidium cardiac PET/CT is likely to be an exciting addition to the European nuclear physician/ cardiologist's radionuclide imaging arsenal.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Positron-Emission Tomography/methods , Rubidium Radioisotopes , Tomography, X-Ray Computed/methods , Ventricular Dysfunction, Left/diagnostic imaging , Adult , Aged , Aged, 80 and over , Coronary Artery Disease/complications , Europe , Humans , Middle Aged , Pilot Projects , Positron-Emission Tomography/trends , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Subtraction Technique , Ventricular Dysfunction, Left/etiology
14.
Nanomedicine (Lond) ; 2(4): 555-67, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17716138

ABSTRACT

AIMS: We recently pioneered the cell electrospinning of living cells as viable biological threads and scaffolds. In that study, we demonstrated the process with an immortalized human brain astrocytoma (1321N1, European Collection of Cell Cultures) cell line at a cell concentration of 10(6) cells/ml. The next stage was to demonstrate the ability to cell electrospin primary living cells at cell concentrations of 10(7) cells/ml (the highest-ever cell concentration threaded by any threading methodology). Furthermore, the post-threaded cells needed their viability assessed over a long period of time by way of flow cytometry, which accurately assesses the viable cell populations. MATERIALS & METHODS: In this work, we employ primary porcine vascular and rabbit aorta smooth-muscle cells prepared as cellular suspensions at cell concentrations of 10(7) cells/ml. The cell electrospinning device employs a coaxial needle arrangement that enables the flow of either highly concentrated cellular suspension in the inner needle while the outer needle accommodates the flow of a viscoelasticity medical-grade polydimethylsiloxane medium. Cell viability was assessed over a long timeframe by way of flow cytometry in comparison with controls. RESULTS & DISCUSSION: The work reported here demonstrates the ability to cell electrospin primary living organisms as highly concentrated cellular suspensions. The viable population of cells post-cell electrospinning are significant and remain viable over both the short and long term, as assessed by flow cytometry. CONCLUSION: Our work elucidates the ability to cell electrospin primary cells as highly concentrated cellular suspensions. The post-cell electrospun organisms are viable over long periods of time, demonstrating a significant active cell population when compared with controls.


Subject(s)
Cell Culture Techniques/methods , Centrifugation/methods , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/physiology , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/physiology , Tissue Engineering/methods , Animals , Cell Aggregation/physiology , Cell Survival , Cells, Cultured , Electrochemistry/methods , Rabbits , Rotation , Swine
15.
Biotechnol J ; 2(5): 622-30, 2007 May.
Article in English | MEDLINE | ID: mdl-17373645

ABSTRACT

Electrohydrodynamic jetting (EHDJ) which is also known as electrosprays (ES) has recently been elucidated as a unique electrified biotechnique for the safe handling and deployment of living organisms. This high intensity electric field driven jetting methodology is now referred to as "bioelectrosprays" (BES). Previously these charged jets have only been shown to jet-process immortalized cells which have undergone expected cellular behavior when compared with control cells. In this paper we demonstrate the ability to jet process primary living organisms in the stable conejetting mode. Finally the viability of the bio-electrosprayed living organisms has been assessed employing a flow cytometry approach which forms the discussion in this paper. Our findings further establish BES as a competing biotechnique, which could be employed for the deposition of primary living organisms according to a predetermined active cellular architecture. One day this could be used for the fabrication of viable tissues and organs for repair or replacement. These advanced studies carried out on BES have direct widespread applications ranging from developmental biology to regenerative and therapeutic medicine, which are a few amongst several other areas of study within the life sciences.


Subject(s)
Biotechnology/methods , Cell Culture Techniques/methods , Electrochemistry/methods , Microfluidics/methods , Specimen Handling/methods , Tissue Culture Techniques/methods , Biotechnology/instrumentation , Biotechnology/trends , Cell Culture Techniques/instrumentation , Cell Culture Techniques/trends , Electrochemistry/instrumentation , Electrochemistry/trends , Microfluidics/instrumentation , Microfluidics/trends , Specimen Handling/instrumentation , Specimen Handling/trends , Technology Assessment, Biomedical , Tissue Culture Techniques/instrumentation , Tissue Culture Techniques/trends
17.
Biomed Mater ; 2(2): 158-68, 2007 Jun.
Article in English | MEDLINE | ID: mdl-18458450

ABSTRACT

We recently demonstrated the ability to use electrified jets under stable conditions for the generation of cell-bearing droplets to the formation of composite threads which are biologically active. Our studies established that processed cells were viable over several generations post-jetting and -threading. These harmless and successful techniques for jet-based cell handling to deployment for precision deposition have great potential and widespread applications in bioengineering and biotechnology. Nonetheless, our investigations into 'bio-electrosprays' and 'cell electrospinning' have elucidated these jets having direct applicability in regenerative and therapeutic medicine to studies in developmental biology. For these very reasons, jet methodologies having the capability to safely handle living organisms for drop and placing are increasingly gaining the interests of life scientists. We now demonstrate yet another technique (a non-electric field-driven approach, previously never explored with jetting living cells), possessing the ability to directly handle the processing of primary living organisms by means of the flow of a cell suspension within a needle placed in a pressure chamber in the presence of an applied pressure difference. The technique we introduce here is referred to as 'aerodynamically assisted bio-jets/-jetting' which is driven completely by aerodynamic forces applied over an exit orifice by way of a differential pressure. Our investigations present an operational window in which stable jetting conditions are achieved for the formation of a near-monodispersed distribution of cell-bearing droplets and droplet residues. Finally, the aerodynamically bio-jetted living primary organisms are assessed (over both short and long time points) for cellular viability by means of FACScan, a flow cytometry technology which quantifies the percentage of living and dead cells. These advanced biophysical and bioengineering studies elucidate the emergence of a non-electric field-driven bio-jetting technology which now joins the cell jetting race.


Subject(s)
Cell Culture Techniques/instrumentation , Cell Separation/instrumentation , Flow Cytometry/instrumentation , Injections, Jet/instrumentation , Microfluidics/instrumentation , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/physiology , Animals , Cell Culture Techniques/methods , Cell Separation/methods , Cells, Cultured , Electrochemistry/instrumentation , Electrochemistry/methods , Equipment Design , Equipment Failure Analysis , Flow Cytometry/methods , Injections, Jet/methods , Microfluidics/methods , Needles , Swine
18.
Biomed Mater ; 2(4): 211-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18458477

ABSTRACT

We recently pioneered the ability to directly electrospin living cells from which scaffolds to membranes were derived. This protocol, now widely referred to as 'cell electrospinning', is currently undergoing in-depth investigations where the post-treated cell's global gene expression to its sub-cellular components is being investigated for understanding any effects post-treating. Our motivation is to develop this method for the biomedical sciences, in particular for applications in regenerative and therapeutic medicine. In the current work, we unveil a direct cell spinning protocol which is non-electric field driven and which will compete directly with cell electrospinning. We referred to this processing method as 'pressure-assisted spinning' in our previous studies, where we demonstrated this route as an emerging micro/nanotechnology. In the current context, we refer to this processing protocol as 'pressure-assisted cell spinning' (PACS). Our developmental studies on PACS reported here show, for the first time, that this technique could be explored as an alternative approach to cell electrospinning. Pressure-assisted cell spinning now enters the direct biological scaffold to membrane formation league.


Subject(s)
Cell Fractionation/instrumentation , Cell Separation/instrumentation , Micromanipulation/instrumentation , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/physiology , Animals , Cell Fractionation/methods , Cell Separation/methods , Cells, Cultured , Equipment Design , Equipment Failure Analysis , Micromanipulation/methods , Rabbits , Rotation
19.
Hum Gene Ther ; 17(7): 717-27, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16839271

ABSTRACT

Somatic gene transfer continues to have potential for the study and therapy of cardiovascular disease. We have developed a modular, self-assembling, nonviral system consisting of Lipofectin, integrin-targeting peptides, and plasmid DNA (LID) and we have applied this to a model of vascular injury, rat carotid angioplasty. Marker gene studies identified transfection of adventitial cells after vector delivery to that layer. Human tissue inhibitor of metalloproteinase-1 (hTIMP-1) was tested as a therapeutic gene product after direct application to the exposed adventitial layer. Vascular LID.hTIMP-1 transfection was confirmed by polymerase chain reaction and gene expression by immunohistochemistry at 7 days. Neointimal areas were 0.160 +/- 0.078 and 0.225 +/- 0.052 mm(2) for LID.hTIMP-1-transfected (n = 14) and LID.pCI-transfected (n = 12) vessels, respectively, at 14 days, and 0.116 +/- 0.068 mm(2) (n = 14) and 0.194 +/- 0.095 mm(2) (n = 14), respectively, at 28 days, representing a 29 and 40% reduction in neointimal hyperplasia at 14 and 28 days, respectively, after balloon dilatation. Neointima-to-media ratios were similarly reduced. In addition, expansile remodeling after balloon injury was inhibited at 14 days, the area within the external elastic lamina being 0.50 +/- 0.02 and 0.61 +/- 0.02 mm(2) in LID.hTIMP-1- and LID.pCI-transfected arteries, respectively (p < 0.0005). We have demonstrated an effective system of therapeutic gene transfer, particularly targeting the arterial adventitia, where transfer of genes involved in matrix remodeling and cell migration may be useful.


Subject(s)
Carotid Artery Injuries/therapy , Genetic Therapy , Genetic Vectors , Tissue Inhibitor of Metalloproteinase-1/genetics , Tunica Intima/pathology , Animals , Carotid Artery Injuries/pathology , Connective Tissue/metabolism , Genetic Vectors/administration & dosage , Genetic Vectors/chemistry , Genetic Vectors/genetics , Hyperplasia/prevention & control , Integrins/metabolism , Peptides/chemistry , Phosphatidylethanolamines/chemistry , Plasmids/chemistry , Rats , Transfection
20.
Biol Psychiatry ; 60(8): 837-42, 2006 Oct 15.
Article in English | MEDLINE | ID: mdl-16780810

ABSTRACT

BACKGROUND: Some cases of acute coronary syndrome (ACS) may be triggered by emotional states such as anger, but it is not known if acute depressed mood can act as a trigger. METHODS: 295 men and women with a verified ACS were studied. Depressed mood in the two hours before ACS symptom onset was compared with the same period 24 hours earlier (pair-matched analysis), and with usual levels of depressed mood, using case-crossover methods. RESULTS: 46 (18.2%) patients experienced depressed mood in the two hours before ACS onset. The odds of ACS following depressed mood were 2.50 (95% confidence intervals 1.05 to 6.56) in the pair-matched analysis, while the relative risk of ACS onset following depressed mood was 4.33 (95% confidence intervals 3.39 to 6.11) compared with usual levels of depressed mood. Depressed mood preceding ACS onset was more common in lower income patients (p = .032), and was associated with recent life stress, but was not related to psychiatric status. CONCLUSIONS: Acute depressed mood may elicit biological responses that contribute to ACS, including vascular endothelial dysfunction, inflammatory cytokine release and platelet activation. Acute depressed mood may trigger potentially life-threatening cardiac events.


Subject(s)
Affect/physiology , Coronary Disease/etiology , Depression/complications , Acute Disease , Aged , Anger/physiology , Coronary Disease/epidemiology , Coronary Disease/physiopathology , Cross-Over Studies , Depression/epidemiology , Depression/physiopathology , Female , Humans , Income , Life Change Events , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Infarction/physiopathology , Risk Factors , Socioeconomic Factors , Sweden/epidemiology
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