5-Hydroxytryptamine Receptors Mediating Carotid and Systemic Haemodynamic Effects: The Relation to Acute Antimigraine Therapy

The presence of a vasoconstrictor substance in blood was suspected for 130 years (Ludwig & Schmidt, 1868) and, 50 years ago, Page and associates at the Cleveland Clinic (Cleveland, Ohio, USA) succeeded in isolating 'serotonin' from the blood (Rapport et al., 1948). Within the next 3 years, the chemical structure of serotonin was deduced (Rapport, 1949) and 5-HT (5-hydroxytryptamine; for other abbreviations see Section 16.4) synthesised (Hamlin & Fischer, 1951; Speeter et al., 1951). Independently, during the 1930s and 40s, Erspamer and colleagues (Rome, Italy), who were interested in characterising the substance imparting characteristic histochemical properties to the enterochromaffin cells of the gastrointestinal mucosa, extracted a basic gut-stimulating factor and named it "enteramine" (Erspamer, 1954). The chemical identity of enteramine with the natural and synthetic serotonin (Erspamer & Asero, 1952) was soon backed by the similarity of pharmacological profile (contraction of sheep carotid artery, guinea-pig, mouse and rabbit jejunum, rat and cat uterus and cat nictitating membrane, triphasic blood pressure response and antagonism by yohimbine and potentiation by cocaine of the sheep carotid artery contraction) (Erspamer, 1954; Page, 1954). Thus, the scene was set for the characterisation of 5-HT receptors

Identification of murine haemopoietic stem cells with monoclonal antibodies

The work described in this thesis deals with the production and application of monoclonal antibodies to characterize murine haemopoietic stem cells. Monoclonal antibodies directed against determinants uniquely expressed on various classes of haemopoietic stem cells should provide valuable tools for analyzing the early differentiation steps in the stem cell compartment at the molecular level, for elucidating the relationhip between the various stem cell classes and for purifying the various stem cell types. In the following chapter the experimental approaches used are described. Chapter 3 deals with attempts to produce stem cell specific monoclonal antibodies. The characterization of the monoclonal antibodies and their possible usefulness in haemopoietic studies are described in chapter 4. Using one of the produced monoclonal antibodies a widely applicable multiparameter flow cytometric procedure for the identification and purification of murine haemopoietic stem cells is described in chapter 5. In chapter 6 various purification procedures for haemopoietic stem cells are compared. It appeared that the highly purified day-12 CFU-S suspensions are heterogeneous, therefore the usefulness of the CFU-S assay as endpoint-assay for pluripotent haemopoietic stem cells is discussed. In the final chapter, the results will be considered in a broader perspective and possible approaches for further study will be outlined

Flexible and efficient IR using array databases

textabstractThe Matrix Framework is a recent proposal by IR researchers to flexibly represent all important information retrieval models in a single multi-dimensional array framework. Computational support for exactly this framework is provided by the array database system SRAM (Sparse Relational Array Mapping) that works on top of a DBMS. Information retrieval models can be specified in its comprehension-based array query language, in a way that directly corresponds to the underlying mathematical formulas. SRAM efficiently stores sparse arrays in (compressed) relational tables and translates and optimizes array queries into relational queries. In this work, we describe a number of array query optimization rules and demonstrate their effect on text retrieval in the TREC TeraByte track (TREC-TB) efficiency task, using the Okapi BM25 model as our example. It turns out that these optimization rules enable SRAM to automatically translate the BM25 array queries into the relational equivalent of inverted list processing including compression, score materialization and quantization, such as employed by custom-built IR systems. The use of the high-performance MonetDB/X100 relational backend, that provides transparent database compression, allows the system to achieve very fast response times with good precision and low resource usage

Sex Differences in Adverse Drug Reactions of Metformin:A Longitudinal Survey Study

Introduction: In general, women more often experience metformin-associated adverse drug reactions (ADRs) than men. Objectives: We aimed to assess whether sex differences in reported ADRs for metformin are observed at different times after initiation, and to explore their concurrence with sex differences in the dose of metformin over time. This may guide future studies in assessing the involved mechanisms of sex differences in metformin-associated ADRs and may guide sex-specific management of ADRs in clinical practice. Methods: This study has a longitudinal design using data about patients initiating metformin collected by the Dutch National Pharmacovigilance Center Lareb through their Intensive Monitoring program. Patients were asked to complete a web-based questionnaire six times after initiation (i.e., at 2 weeks, 6 weeks and at 3, 6, 9, and 12 months). The outcome variables were the proportion of patients reporting any ADR (primary) and the dose of metformin (secondary). Sex differences in the proportions of ADRs and in the dose were tested at each assessment using Pearson Chi-Squared tests and Wilcoxon rank-sum tests, respectively. Using Bonferroni adjustment for multiple testing, a p value < 0.01 was considered statistically significant. Results: The number of included patients was 1712 (40.9% women). Women reported an ADR more often than men, which was statistically significant at the assessment at 2 weeks (34% vs 25%, p < 0.001), and 6 weeks (37% vs 28%, p = 0.001) after initiation. In general, women were reported to be prescribed a lower dose than men, which became statistically significant at the 9-month assessment (p < 0.01). Conclusions: Sex differences in reported ADRs were seen in the first weeks after metformin initiation, whereas statistically significant differences in self-reported prescribed dosing were observed after several months. Patients, in particular women, might benefit from being prescribed lower metformin doses at treatment initiation

Investigating the reliability and validity of the Dutch versions of the illness management and recovery scales among clients with mental disorders

Background: The Illness Management and Recovery scales (IMRS) can measure the progress of clients’ illness self-management and recovery. Previous studies have examined the psychometric properties of the IMRS. Aims: This study examined the reliability and validity of the Dutch version of the IMRS. Method: Clients (n = 111) and clinicians (n = 40) completed the client and clinician versions of the IMRS, respectively. The scales were administered again 2 weeks later to assess stability over time. Validity was assessed with the Utrecht Coping List (UCL), Dutch Empowerment Scale (DES), and Brief Symptom Inventory (BSI). Results: The client and clinician versions of the IMRS had moderate internal reliability, with α = 0.69 and 0.71, respectively. The scales showed strong test–retest reliability, r = 0.79, for the client version and r = 0.86 for the clinician version. Correlations between client and clinician versions ranged from r = 0.37 to 0.69 for the total and subscales. We also found relationships in expected directions between the client IMRS and UCL, DES and BSI, which supports validity of the Dutch version of the IMRS. Conclusions: The Dutch version of the IMRS demonstrated good reliability and validity. The IMRS could be useful for Dutch-speaking programs interested in evaluating client progress on illness self-management and recovery

Highly Efficient Semi-Continuous Extraction and In-Line Purification of High β-O-4 Butanosolv Lignin

Innovative biomass fractionation is of major importance for economically competitive biorefineries. Lignin is currently severely underutilized due to the use of high severity fractionation methodologies that yield complex condensed lignin that limits high-value applicability. Mild lignin fractionation conditions can lead to lignin with a more regular C-O bonded structure that has increased potential for higher value applications. Nevertheless, such extraction methodologies typically suffer from inadequate lignin extraction efficiencies and yield. (Semi)-continuous flow extractions are a promising method to achieve improved extraction efficiency of such C-O linked lignin. Here we show that optimized organosolv extraction in a flow-through setup resulted in 93-96% delignification of 40 g walnut shells (40 wt% lignin content) by applying mild organosolv extraction conditions with a 2 g/min flowrate of a 9:1 n-butanol/water mixture with 0.18 M H2SO4 at 120°C in 2.5 h. 85 wt% of the lignin (corrected for alcohol incorporation, moisture content and carbohydrate impurities) was isolated as a powder with a high retention of the β-aryl ether (β-O-4) content of 63 linking motifs per 100 C9 units. Close examination of the isolated lignin showed that the main carbohydrate contamination in the recovered lignin was butyl-xyloside and other butoxylate carbohydrates. The work-up and purification procedure were investigated and improved by the implementation of a caustic soda treatment step and phase separation with a continuous integrated mixer/separator (CINC). This led to a combined 75 wt% yield of the lignin in 3 separate fractions with 3% carbohydrate impurities and a very high β-O-4 content of 67 linking motifs per 100 C9 units. Analysis of all the mass flows showed that 98% of the carbohydrate content was removed with the inline purification step, which is a significant improvement to the 88% carbohydrate removal for the traditional lignin precipitation work-up procedure. Overall we show a convenient method for inline extraction and purification to obtain high β-O-4 butanosolv lignin in excellent yields

Frailty and functional outcomes after open and endovascular procedures for patients with peripheral arterial disease:A systematic review

Background: Frailty has been associated with postoperative complications and mortality across surgical specialties, including vascular surgery. However, the influence of frailty on postoperative functional outcomes is unclear. We sought to determine the influence of frailty on functional outcomes after open or endovascular vascular procedures in patients with peripheral arterial disease. Methods: This systematic review was conducted according to the PRISMA guidelines. Eligible articles were identified through database searches of Pubmed and EMBASE in April 2017. Studies reporting on frailty and functional outcomes after vascular interventions for peripheral artery disease (PAD) were included. Outcomes of interest were dependency in activities of daily living (ADL), dependent mobility, discharge destination, disability-free survival, and quality of life. Individual studies were assessed for quality and risk of bias using the Quality in Prognosis Studies tool. Results: Eight studies met the eligibility criteria and were included. The risk of bias was low in two studies, intermediate in three studies, and high in three studies. Methods for frailty assessment were different for each study. Frailty was a predictor for discharge to a higher level of care, dependent mobility, and dependency in ADL after vascular procedures for PAD. Both frailty models and individual frailty characteristics seem to be associated with these adverse functional outcomes. Conclusions: Despite a limited amount of literature and an overall intermediate quality of the included studies, this systematic review shows an association between frailty and adverse functional outcomes after peripheral arterial procedures for PAD, including discharge to a care facility, dependent mobility, and a decline in ADL functioning

Комбинированная кинезотерапия в лечении больных коксартрозом

Вивчені результати лікування 54 пацієнтів з коксартрозом. Включення комплексного лікування даного контингенту пацієнтів комбінованої кінезотерапії методикою Євмінова дозволяє підвищити ефективність проведеної терапії.This article studied results of treatment of 54 patients with coxarthrosis. Upon inclusion of the combined kinesitherapy under Evminov method into the complex treatment of the mentioned group of patients it became possible to increase the effectiveness of the whole therapy