Ian Miller

Effect of Surface Wettability and Topography on the Adhesion of Osteosarcoma Cells on Plasma-modified Polystyrene

Biomaterials interact with the biological environment at their surface, making accurate biophysical characterization of the surface crucially important for understanding subsequent biological effects. In this study, the surface of polystyrene (PS) was systematically altered in order to determine the effect of plasma treatment and surface roughness on cell adhesion and spreading. Surfaces with water contact angle from hydrophilic (12°) to superhydrophobic (155°) were obtained through a combination of modifying surface roughness (R a), the deposition of siloxane coatings and the fluorination of the PS surface. R a values in the range of 19—2365 nm were obtained by grinding the PS surface. The nanometer-thick siloxane coatings were deposited using an atmospheric pressure plasma system, while the fluorination of the PS was carried out using a low-pressure radio frequency (RF) plasma. The siloxane coatings were obtained using a liquid poly(dimethylsiloxane) precursor that was nebulized into helium or helium/oxygen plasmas. Water contact angles in the range of 12—122° were obtained with these coatings. Cell adhesion studies were carried out using human MG63 osteosarcoma cells. It was observed that higher polymer surface roughness enhanced cell adhesion, but had a negative effect on cell spreading. Optimum cell adhesion was observed at ∼64° for the siloxane coatings, with a decrease in adhesion observed for the more hydrophilic and hydrophobic coatings. This decrease in cell adhesion with an increase in hydrophobicity was also observed for the fluorinated PS surfaces with water contact angles in the range of 110—155°.

Detection and quantification of leptospires in urine of dogs: a maintenance host for the zoonotic disease leptospirosis

Leptospirosis is a global zoonotic disease. Pathogenic Leptospira species, the causative agent of leptospirosis, colonize the renal tubules of chronically infected maintenance hosts such as dogs, rats and cattle. Maintenance hosts typically remain clinically asymptomatic and shed leptospires into the environment via urine. In contrast, accidental hosts such as humans can suffer severe acute forms of the disease. Infection results from direct contact with infected urine or indirectly, through contaminated water sources. In this study, a quantitative real-time PCR specific for lipL32 was designed to detect the urinary shedding of leptospires from dogs. The sensitivity and specificity of the assay was evaluated using both a panel of pathogenic Leptospira species and clinical microbial isolates, and samples of urine collected from experimentally infected rats and non-infected controls. The lower limit of detection was approximately 3 genome equivalents per reaction. The assay was applied to canine urine samples collected from local dog sanctuaries and the University Veterinary Hospital (UVH) at University College Dublin. Of 525 canine urine samples assayed, 37 were positive, indicating a prevalence of urinary shedding of leptospires of 7.05%. These results highlight the need to provide effective canine vaccination strategies and raise public health awareness.

Leptospirosis: risks during recreational activities.

Rats, dogs, cattle, bats and sea lions, exemplify the diversity of mammalian species that can facilitate transmission of the zoonotic disease leptospirosis. The causative agent, pathogenic species of Leptospira, is shed in urine of chronically infected hosts. Direct contact with infected urine, or indirectly with water sources contaminated with infected urine, poses a risk of infection for humans exposed during water‐related recreational and occupational activities. New serovars of Leptospira and maintenance hosts continue to be identified. In the western world, incidences of recreational exposure are increasing, while incidences of occupational exposure are decreasing. Adventure travellers returning from tropical regions, are presenting at clinics with symptoms of leptospirosis following participation in high risk activities including white water rafting, triathlons, endurance races and caving. Risks of infection can be reduced with increased awareness of how the disease is contracted, by avoiding contact with high risk water sources and the use of prophylaxis during high risk activities. Molecular techniques can be used to provide risk assessments prior to competition, to supplement epidemiology, and to assess shedding of Leptospira in urine samples.

Comparative Proteomic Analysis of Differentially Expressed Proteins in the Urine of Reservoir Hosts of Leptospirosis

Rattus norvegicus is a natural reservoir host for pathogenic species of Leptospira. Experimentally infected rats remain clinically normal, yet persistently excrete large numbers of leptospires from colonized renal tubules via urine, despite a specific host immune response. Whilst persistent renal colonization and shedding is facilitated in part by differential antigen expression by leptospires to evade host immune responses, there is limited understanding of kidney and urinary proteins expressed by the host that facilitates such biological equilibrium. Urine pellets were collected from experimentally infected rats shedding leptospires and compared to urine from non-infected controls spiked with in vitro cultivated leptospires for analysis by 2-D DIGE. Differentially expressed host proteins include membrane metallo endopeptidase, napsin A aspartic peptidase, vacuolar H+ATPase, kidney aminopeptidase and immunoglobulin G and A. Loa22, a virulence factor of Leptospira, as well as the GroEL, were increased in leptospires excreted in urine compared to in vitro cultivated leptospires. Urinary IgG from infected rats was specific for leptospires. Results confirm differential protein expression by both host and pathogen during chronic disease and include markers of kidney function and immunoglobulin which are potential biomarkers of infection.

Surface-induced cell signaling events control actin rearrangements and motility.

Understanding the interrelationship between material surface properties and the biological response to such materials remains a fundamental scientific challenge, as well as being of considerable practical importance in medicine. Through the use of a homologous series of copolymers of increasing hydrophobicity, we aimed to illuminate the interplay between material surface hydrophobicity and signalling events within cells in contact with this model system. Extending previous work, we hereby unravel key pathways controlling cell motility and the formation of a stellate phenotype, following interaction with polymer-coated surfaces. We reveal a comparative increase in cellular motility with increasing surface hydrophilicity, conjoint with an arrest in cell cycle progression. We also show an anomalous turnover of actin within the cell as a function of changing surface hydrophobicity. Finally, we show that cyclic adenosine monophosphate may be an effector of the cellular phenotype, as its production is increased in response to changes in the surface properties. These results highlight important signaling events which control actin rearrangements and the subsequent motility and its effectors.

Necessary Torture?: Vivisection, Suffragette Force-Feeding, and Responses to Scientific Medicine in Britain c. 1870–1920

One of the primary aims of late nineteenth-century laboratory experimentation was to ground understandings of illness and disease within new regimes of science. It was also hoped that clinical practice would become increasingly complemented by discoveries and technologies accrued from emergent forms of modern medical enquiry, and that, ultimately, this would lead to improved diagnostic and therapeutic procedures that could be applied to a wide variety of medical complaints. This met with resistance in Britain. So far, analyses of the British reception to forms of scientific medicine have focused on a science versus intuition dichotomy. This article aims to address other aspects intertwined in the debate through an exploration of alternative representations of the medical scientist available and the relation of this to perceptions of clinical practice. Using new technologies of the stomach as a case study, I shall examine how physiologists approached digestion in the laboratory, the responses of antivivisectionists to this, the application of gastric innovations at the clinical level, and the impact of the use of the stomach tube in the suffragette force-feeding controversy.

The mind and stomach at war: stress and abdominal illness in Britain c.1939-1945.

Medical professionals are often obliged to engage with unforeseen problems during times of conflict. These typically emerge and develop unpredictably, giving rise to spates of internal biological disorders that may affect specific body areas or induce problematic forms of psychological behaviour. The phenomena of shell shock and Gulf War syndrome are prominent historical examples of these, both being conditions not usually witnessed during peacetime. However, conflict can also generate changes in pre-existing medical complaints. In this article, I suggest that Britain experienced unexpected changes in abdominal problems during the Second World War. An alarming increase in gastric ailments, most notably dyspepsia, peptic ulcer and duodenal ulcer, was noted from the start of the conflict. There was rising concern in both the government and the medical profession about the anticipated drain on national manpower and military efficiency. I shall relate this to the wider process of the incorporation of psychological medicine into the treatment of conditions of the gastrointestinal tract.More generally, this paper expands upon suggestions that there exists a wide range of chronic disorders that are of potential importance to historians of medicine. In 1979, G H Brieger complained that the significance of the problematic condition of dyspepsia, or indigestion, had been greatly underrated despite the usefulness that a careful study of it would hold for the enhancement of historical understandings of medical theory and practice. However, little else was published on the history of stomach problems until eighteen years later when William F Bynum argued a similar case in Gastroenterology in Britain (1997), an edited volume compiled with the specific aim of outlining some of the area’s main individuals, issues and technical developments. He anticipated that future scholars would expand upon what he considered to be a highly significant, if complex, theme. However, to date, such research has been limited. This article therefore provides one example of how the many experiences of the stomach and its illnesses have occupied prominent positions in society, culture and medicine by locating this organ at the centre of both medical and popular wartime imagination.

A Novel Positron Emission Tomography (PET) Approach to Monitor Cardiac Metabolic Pathway Remodeling in Response to Sunitinib Malate.

Sunitinib is a tyrosine kinase inhibitor approved for the treatment of multiple solid tumors. However, cardiotoxicity is of increasing concern, with a need to develop rational mechanism driven approaches for the early detection of cardiac dysfunction. We sought to interrogate changes in cardiac energy substrate usage during sunitinib treatment, hypothesising that these changes could represent a strategy for the early detection of cardiotoxicity. Balb/CJ mice or Sprague-Dawley rats were treated orally for 4 weeks with 40 or 20 mg/kg/day sunitinib. Cardiac positron emission tomography (PET) was implemented to investigate alterations in myocardial glucose and oxidative metabolism. Following treatment, blood pressure increased, and left ventricular ejection fraction decreased. Cardiac [18F]-fluorodeoxyglucose (FDG)-PET revealed increased glucose uptake after 48 hours. [11C]Acetate-PET showed decreased myocardial perfusion following treatment. Electron microscopy revealed significant lipid accumulation in the myocardium. Proteomic analyses indicated that oxidative metabolism, fatty acid β-oxidation and mitochondrial dysfunction were among the top myocardial signalling pathways perturbed. Sunitinib treatment results in an increased reliance on glycolysis, increased myocardial lipid deposition and perturbed mitochondrial function, indicative of a fundamental energy crisis resulting in compromised myocardial energy metabolism and function. Our findings suggest that a cardiac PET strategy may represent a rational approach to non-invasively monitor metabolic pathway remodeling following sunitinib treatment.

Reforming food in post-Famine Ireland: Medicine, science and improvement, 1845–1922

Reforming food in post-famine Ireland: Medicine, science and improvement, 1845-1922 is the first dedicated study of how and why Irish eating habits dramatically transformed between the famine and independence. It also investigates the simultaneous reshaping of Irish food production after the famine. Adopting an interdisciplinary approach, the book draws from the diverse methodological disciplines of medical history, history of science, cultural studies, Irish studies, gender studies and food studies. Making use of an impressive range of sources, it maps the pivotal role of food in the shaping of Irish society onto a political and social backdrop of famine, Land Wars, political turbulence, the First World War and the struggle for independence. It will be of interest to historians of medicine and science as well as historians of modern Irish social, economic, political and cultural history.

The Chemistry of Famine: Nutritional Controversies and the Irish Famine, c.1845–7

The activities of Irish medical practitioners in relieving the impact of the Irish Famine (c.1845–52) have been well documented. However, analysis of the function of contemporary medico-scientific ideas relating to food has remained mostly absent from Famine historiography. This is surprising, given the burgeoning influence of Liebigian chemistry and the rising social prominence of nutritional science in the 1840s. Within this article, I argue that the Famine opened up avenues for advocates of the social value of nutritional science to engage with politico-economic discussion regarding Irish dietary, social and economic transformation. Nutritional science was prominent within the activities of the Scientific Commission, the Central Board of Health and in debates regarding soup kitchen schemes. However, the practical inefficacy of many scientific suggestions resulted in public associations being forged between nutritional science and the inefficiencies of state relief policy, whilst emergent tensions between the state, science and the public encouraged scientists in Ireland to gradually distance themselves from state-sponsored relief practices.