Coating stent materials with polyhedral oligomeric silsesquioxane-poly(carbonateurea)urethane nanocomposites

The long-term efficacy of coronary or peripheral stenting is limited by in-stent restenosis (ISR), which occurs in 15 to 30% of patients and is attributed primarily to neointimal hyperplasia. By adding a drug-eluting coating, this rate has been reduced to about 5% or less. However, recently longer-term follow-up data has highlighted problems with drug-coated stents, including late stage thrombosis. A bio-stable poly(carbonate-urea)urethane has been used for stent coating and the surface properties of the polymer have been optimised by incorporating the polyhedral oligomeric silsesquioxane molecule. These POSS polymers improve the adhesion and the growth of endothelial cells. The work described in this thesis, presents an innovative approach in self-expanding/balloon expandable coronary stent design that incorporates a NiTi/stainless steel alloy scaffold with a polyhedral oligomeric silsesquioxane- poly (carbonate-urea) urethane nanocomposite polymer (POSS-PCU) coating. Electrohydrodynamic spraying and ultrasonic atomization spraying of the non-biodegradable nanocomposite polyhedral oligomeric silsesquioxane (POSS) polymer have been investigated in detail for coating metallic stent materials and compared with dip coating. Because of the tight geometry of coronary stents, these new coating techniques have been shown to offer advantages over traditional coating techniques. These advantages include, reduced polymer consumption, precise coating thickness as low as 10 μm and a highly controllable spray which leads to consistent reproducible results. However, poor adhesion, or bond deterioration over the lifespan/ deployment of the device could reduces the efficiency and could impart even more complexity to the implant including formation of debris which can induce thrombus formation. Changing the surface physical property/chemical composition through the proposed protocol has been shown to increase the bonding strength by up to three times. This study has identified a new process and conditions which can be used in stent coating research

Systemic enzyme therapy in chronic venous disease: a review

Chronic venous disease (CVD), a sequel of venous insufficiency, has great medical and socioeconomic impact. Varicose veins and venous ulcer are amongst its commonest manifestations. In CVD, incompetent valves, weakened vascular walls, venous hypertension and increased permeability of venous walls lead to the release of proinflammatory mediators like tumor necrosis factor (TNF)-α, interleukin (IL)-1β, reactive oxygen species (R.O.S.), and reactive nitrogen species (R.N.S.) in the venous milieu. Pharmacotherapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is often used to relieve pain caused by venous disease. However, there is a need for therapies that target the microcirculatory disorders and act on chronic inflammatory processes. Systemic enzyme therapy (SET), with orally administered combination of proteolytic enzymes- trypsin, bromelain, and flavonoid rutoside, has been used since decades for their anti-inflammatory, analgesic, anti-edematous, antithrombotic and antioxidant properties. This review discusses the various relevant pharmacodynamic properties demonstrated by the ingredients, followed by clinical studies of SET, which have demonstrated benefit in both subjective and objective parameters. These studies indicate that SET has good efficacy, tolerability and holds great promise to improve the quality of life of a patient with CVD.  

Transducer degrees: atoms, infima and suprema

Although finite state transducers are very natural and simple devices, surprisingly little is known about the transducibility relation they induce on streams (infinite words). We collect some intriguing problems that have been unsolved since several years. The transducibility relation arising from finite state transduction induces a partial order of stream degrees, which we call Transducer degrees, analogous to the well-known Turing degrees or degrees of unsolvability. We show that there are pairs of degrees without supremum and without infimum. The former result is somewhat surprising since every finite set of degrees has a supremum if we strengthen the machine model to Turing machines, but also if we weaken it to Mealy machines

Progression of Coronary Artery Calcium and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

BackgroundAlthough the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi-Ethnic Study of Atherosclerosis.Methods and resultsThe Multi-Ethnic Study of Atherosclerosis is a population-based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi-Ethnic Study of Atherosclerosis participants who had baseline and follow-up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2 years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow-up of 9.6 (interquartile range: 8.8-10.6) years, 182 participants developed incident HF. CAC progression of 10 units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease (P=0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (β=0.16; P=0.03) and LV end systolic volume (β=0.12; P=0.006) after excluding participants with any coronary heart disease.ConclusionsCAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow-up exam independent of overt coronary heart disease

Analysis of glutathione S-transferase (M1, T1 and P1) gene polymorphisms in Iranian prostate cancer subjects

Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of prostate cancer in various populations. The current study was done with Iranian subjects to evaluate the association of the polymorphism of glutathione S-transferase subtypes (T, M and P) and the susceptibility of prostate cancer in Iranian patients as compared to controls. Blood samples were collected from 65 prostate cancer patients and 65 unrelated health individuals as controls from Milad hospital, Tehran, Iran. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the polymorphism of glutathione S-transferase pi (GSTP1) -313 A/G gene, while multiplex PCR method was utilized to detect the glutathione S-transferase teta (GSTT) 1 and glutathione S-transferase mμ (GSTM) 1 null allele. There was no significant association in the -313 G allele (Val) of GSTP1 gene  olymorphism and prostate cancer risk (odds ratio 0.61, 95% confidence intervals (CI) 0.08 - 4.60, p = 0.627). Moreover, no relationship was found between the polymorphism of GSTT1 (odds ratio 0.66, 95% CI 0.27 - 1.62) and GSTM1 (odds ratio 0.54, 95% CI 0.27 - 1.08) genes and higher risk of prostate cancer among Iranian subjects (p > 0.05). This study showed that either GSTP1-313 G polymorphism or GSTT1 and GSTM1 genes cannot be predisposing risk factors for prostate cancer among Iranian subjects.Key words: Glutathione S-transferase, prostate cancer, polymorphism

Construction of an Interface Terminology on SNOMED CT Generic Approach and Its Application in Intensive...

Objective: To provide a generic approach for developing a domain-specific interface terminology on SNOMED CT and to apply this approach to the domain of intensive care. Methods:The process of developing an interface terminology on SNOMED CT can be regarded as six sequential phases: domain analysis, mapping from the domain con - cepts to SNOMED CT concepts, creating the SNOMED CT subset guided by the mapping, extending the subset with non-covered concepts, constraining the subset by removing irrelevant content, and deploying the subset in a terminology server. Results:The APACHE IV classification, a standard in the intensive care with 445 diagnostic categories, served as the starting point for designing the interface terminology. The majority (89.2%) of the diagnostic categories from APACHE IV could be mapped to SNOMED CT concepts and for the remaining concepts a partial match was identified. The resulting initial set of mapped concepts consisted of 404 SNOMED CT concepts. This set could be extended to 83,125 concepts if all taxonomic children of these concepts were included. Also including all concepts that are referred to in the definition of other concepts lead to a subset of 233,782 concepts. An evaluation of the interface terminology should reveal what level of detail in the subset is suitable for the intensive care domain and whether parts need further constraining. In the final phase, the interface terminology is implemented in the intensive care in a locally developed terminology server to collect the reasons for intensive care admission. Conclusions: We provide a structure for the process of identifying a domain-specific interface terminology on SNOMED CT. We use this approach to design an interface terminology on SNOMED CT for the intensive care domain. This work is of value for other researchers who intend to build a domain-specific interface terminology on SNOMED CT