Characterization of the Binding Properties of Molecularly Imprinted Polymers

The defining characteristic of the binding sites of any particular molecularly imprinted material is heterogeneity: that is, they are not all identical. Nonetheless, it is useful to study their fundamental binding properties, and to obtain average properties. In particular, it has been instructive to compare the binding properties of imprinted and non-imprinted materials. This chapter begins by considering the origins of this site heterogeneity. Next, the properties of interest of imprinted binding sites are described in brief: affinity, selectivity, and kinetics. The binding/adsorption isotherm, the graph of concentration of analyte bound to a MIP versus concentration of free analyte at equilibrium, over a range of total concentrations, is described in some detail. Following this, the techniques for studying the imprinted sites are described (batch-binding assays, radioligand binding assays, zonal chromatography, frontal chromatography, calorimetry, and others). Thereafter, the parameters that influence affinity, selectivity and kinetics are discussed (solvent, modifiers of organic solvents, pH of aqueous solvents, temperature). Finally, mathematical attempts to fit the adsorption isotherms for imprinted materials, so as to obtain information about the range of binding affinities characterizing the imprinted sites, are summarized

Self-Assembly and Host–Guest Interactions of Pd3L2 Metallo-cryptophanes with Photoisomerizable Ligands

New photoswitchable pyridyl-azo-phenyl-decorated tripodal host ligands (Laz) that belong to the cyclotriveratrylene family have been synthesized, and their photoswitching behavior and crystal structures determined. The latter includes a remarkable 7-fold Borromean-weave entanglement of π–π stacked layers. Trigonal bipyramidal {[Pd(en)]3(Laz)2}6+ metallo-cryptophanes (en = ethylenediamine) were formed from these and a previously known pyridyl-azo-phenyl-decorated tripodal host ligand. These coordination cages dissociate at low concentrations and are less robust to photoswitching of the Laz ligands than were previously reported Ir(III)-linked metallo-cryptophanes with similar ligands, reflecting the greater lability of the Pd–N bonds. The {[Pd(en)]3(Laz)2}6+ cages all act as hosts, binding octyl sulfate anions, or N-[2-(dimethylamino)ethyl]-1,8-naphthalimide in a dimethyl sulfoxide solution

Synthesis and organogelating behaviour of amino acid-functionalised triphenylenes

Four novel amino acid-functionalised triphenylenes have been prepared with glycine, L-alanine, L-phenylalanine and L-tryptophan ethyl ester side-chains. The glycine derivative is a good gelator of chloroform, the alanine derivative gels ethanol and toluene, and the phenylalanine derivative gels benzene and toluene. The tryptophan derivative does not gel any of the solvents tested, most probably due to its more bulky structure, but forms microspheres by evaporation-induced self-assembly. The self-assembly properties of the π-gelators have been investigated using infrared, UV-absorption and fluorescence spectroscopy, concentration- and temperature-dependent NMR, and X-ray scattering experiments on dried xerogel as well as the wet organogel. The latter experiments suggest the glycine gel in chloroform includes columnar aggregates, with an overall disordered columnar oblique mesophase. These compounds are of interest because of the well-known hole-transporting properties of triphenylene liquid crystals: 1-D columnar assemblies of these compounds may find applications in organic electronic devices

Spontaneous intra-peritoneal bleeding secondary to warfarin, presenting as an acute appendicitis: a case report and review of literature

BACKGROUND: Warfarin is a coumarin anti-coagulant, used widely for the therapeutic and prophylactic anticoagulation. Although, it is considered as a life saving medicine, it is associated with the significant adverse effects including intra-abdominal bleeding, which have been very well documented in literature. However, the presentation of warfarin induced intra-peritoneal bleeding as an acute appendicitis has not been reported in English literature. We report this rare, spontaneous intra-peritoneal bleeding secondary to warfarin therapy, mimicking the signs and symptoms of an acute appendicitis for the first time in English literature. CASE PRESENTATION: A 41 year-old female patient who was on warfarin for prophylaxis following the previous episode of pulmonary embolism, presented to the Casualty with the typical symptoms of an acute appendicitis. During operative intervention, we found it to be the spontaneous intra-peritoneal bleeding secondary to warfarin. The patient recovered well following the operation. CONCLUSION: We recommend the use of the radiological investigations in all the cases of acute abdomen who are on warfarin even if the INR is within the therapeutic range

A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma

The phosphatidylinositol 3-kinase signal transduction pathway members are often activated in tumor samples from patients with non-Hodgkin's lymphoma (NHL). Everolimus is an oral agent that targets the raptor mammalian target of rapamycin (mTORC1). The goal of this trial was to learn the antitumor activity and toxicity of single-agent everolimus in patients with relapsed/refractory aggressive NHL. Patients received everolimus 10 mg PO daily. Response was assessed after two and six cycles, and then every three cycles until progression. A total of 77 patients with a median age of 70 years were enrolled. Patients had received a median of three previous therapies and 32% had undergone previous transplant. The overall response rate (ORR) was 30% (95% confidence interval: 20–41%), with 20 patients achieving a partial remission and 3 a complete remission unconfirmed. The ORR in diffuse large B cell was 30% (14/47), 32% (6/19) in mantle cell and 38% (3/8) in follicular grade 3. The median duration of response was 5.7 months. Grade 3 or 4 anemia, neutropenia and thrombocytopenia occurred in 14, 18 and 38% of patients, respectively. Everolimus has single-agent activity in relapsed/refractory aggressive NHL and provides proof-of-concept that targeting the mTOR pathway is clinically relevant

Education and practice gaps on atrial fibrillation and anticoagulation: a survey of cardiovascular nurses

BACKGROUND: Patients’ knowledge of their atrial fibrillation (AF) and anticoagulation therapy are determinants of the efficacy of thromboprophylaxis. Nurses may be well placed to provide counselling and education to patients on all aspects of anticoagulation, including self-management. It is important that nurses are well informed to provide optimal education to patients. Current practice and knowledge of cardiovascular nurses on AF and anticoagulation in the Australian and New Zealand (ANZ) context is not well reported. This study aimed to; 1) Explore the nurse’s role in clinical decision making in anticoagulation in the setting of AF; 2) Describe perceived barriers and enablers to anticoagulation in AF; 3) Investigate practice patterns in the management of anticoagulation in the ANZ setting; 4) Assess cardiovascular nurses’ knowledge of anticoagulation. METHODS: A paper-based survey on current practices and knowledge of AF and anticoagulation was distributed during the Australian Cardiovascular Nursing College (ACNC) Annual Scientific Meeting, February 2014. This survey was also emailed to Cardiovascular Trials Nurses throughout New South Wales, Australia and nursing members of the Cardiac Society of Australia and New Zealand (CSANZ). RESULTS: There were 41/73 (56 %) respondents to the paper-based survey. A further 14 surveys were completed online via nurse members of the CSANZ, and via an investigator developed NSW cardiovascular trials nurse email distribution list. A total of 55 surveys were completed and included in analyses. Prior education levels on AF, stroke risk, anticoagulation and health behaviour modification were mixed. The CHA(2)DS(2)VASc and HAS-BLED risk stratification tools were reported to be underused by this group of clinicians. Reported key barriers to anticoagulation included; fears of patients falling, fears of poor adherence to medication taking and routine monitoring. Patient self-monitoring and self-management were reported as underutilised. ANZ cardiovascular nurses reported their key role to be counselling and advising patients on therapy regimens. Anticoagulant-drug interaction knowledge was generally poor. CONCLUSION: This study identified poor knowledge and practice in the areas of AF and anticoagulation. There is scope for improvement for cardiovascular nurses in ANZ in relation to AF and anticoagulation knowledge and practice

Views on primary prevention of cardiovascular disease - an interview study with Swedish GPs

Background: General practitioners (GPs) have gradually become more involved in the prevention of cardiovascular disease (CVD), both through more frequent prescribing of pharmaceuticals and by giving advice regarding lifestyle factors. Most general practitioners are now faced with decisions about pharmaceutical or non-pharmaceutical treatment for primary prevention every day. The aim of this study was to explore, structure and describe the views on primary prevention of cardiovascular disease in clinical practice among Swedish GPs. Methods: Individual interviews were conducted with 21 GPs in southern Sweden. The interview transcripts were analysed using a qualitative approach, inspired by phenomenography. Results: Two main categories of description emerged during the analysis. One was the degree of reliance on research data regarding the predictability of real risk and the opportunities for primary prevention of CVD. The other was the allocation of responsibility between the patient and the doctor. The GPs showed different views, from being convinced of an actual and predictable risk for the individual to strongly doubting it; from relying firmly on protection from disease by pharmaceutical treatment to strongly questioning its effectiveness in individual cases; and from reliance on prevention of disease by non-pharmaceutical interventions to a total lack of reliance on such measures. Conclusions: The GPs' different views, regarding the rationale for and practical management of primary prevention of CVD, can be interpreted as a reflection of the complexity of patient counselling in primary prevention in clinical practice. The findings have implications for development and implementation of standard treatment guidelines, regarding long-time primary preventive treatment

Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy

The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus) have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of advanced renal cell carcinoma (RCC). Everolimus is an oral agent that has recently obtained US FDA and EMEA approval for the treatment of advanced RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not yet approved for any indication. The use of mTOR inhibitors, either alone or in combination with other anticancer agents, has the potential to provide anticancer activity in numerous tumor types. Cancer types in which these agents are under evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma, hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial cancer, and non-small-cell lung cancer. The results of ongoing clinical trials with mTOR inhibitors, as single agents and in combination regimens, will better define their activity in cancer

Preventing crime in cooperation with the mental health care profession

Although major mental disorders do not have a central position in many criminological theories, there seems to be an evident relationship between these disorders and criminal behavior. In daily practice police officers and mental health care workers work jointly to prevent nuisance and crime and to keep the city livable. Examining the situations where the criminal justice system and mental health institutes are jointly involved to prevent crime, some pitfalls emerge that seem to threaten successful cooperation. There appear to be unrealistic expectations of the possibility to reduce the risk of reoffending by means of treatment and of the possibility to predict which offender poses a risk to society. Another complexity is the fact that both parties work from different backgrounds and pursue different goals. The way society and the criminal justice system deal with persons who are assumed to be a risk to the community because of a mental disorder demands a further investigation from a criminological perspective

GAMEC – a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours

There is no consensus as to the management of untreated poor prognosis or relapsed/refractory germ cell tumours. We have studied an intensive cisplatin-based regimen that incorporates high-dose methotrexate (HD MTX) and actinomycin-D and etoposide every 14 days (GAMEC). Sixty-two patients were enrolled in a phase 2 study including 27 who were untreated (IGCCCG, poor prognosis) and 35 with progression despite conventional platinum based chemotherapy. The pharmacokinetics of the drugs were correlated with standard outcome measures. Twenty of the untreated patients were progression free following GAMEC and appropriate surgery, as were 18 individuals in the pretreated group. None of the established prognostic factors for therapy for pretreated patients could identify a poor-prognosis group. Five out of nine late relapses to prior chemotherapy were progression free following GAMEC and appropriate surgery. All patients had at least one episode of febrile neutropenia and there were five (8%) treatment-related deaths. PK values were not predictive of efficacy or toxicity, although the dose intensity in the pretreated group of patients, especially of HD MTX, was significantly correlated with progression-free survival (PFS). GAMEC is a novel intensive regimen for this group of patients producing encouraging responses, although with significant toxicity. For those in whom it fails, further therapy is still possible with durable responses being seen