Livres sur le sujet « Protein analogue »

In all patients with chronic kidney disease (CKD) stages 3–5, regular monitoring of serum markers of CKD-mineral and bone disorder, including calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 25-hydroxyvitamin D, and alkaline phosphatase, is recommended. Target ranges for these markers are endorsed by guidelines. The principles of therapy for secondary hyperparathyroidism include control of hyperphosphataemia, correction of hypocalcaemia, use of vitamin D sterols, use of calcimimetics, and parathyroidectomy. of hyperphosphataemia is crucial and may be achieved by means of dietary P restriction, use of P binders, and P removal by dialysis. Dietary P restriction requires caution, as it may be associated with protein malnutrition. Aluminium salts are effective P binders, but they are not recommended for long-term use, as Aluminium toxicity (though from contaminated dialysis water rather than oral intake) may cause cognitive impairment, osteomalacia, refractory microcytic anaemia, and myopathy. Ca-based P binders are also quite effective, but should be avoided in patients with hypercalcaemia, vascular calcifications, or persistently low PTH levels. Non-aluminium, non-Ca binders, like sevelamer and lanthanum carbonate, may be more adequate for such patients; however, they are expensive and may have several side effects. Furthermore, comparative trials have failed so far to provide conclusive evidence on the superiority of these newer P binders over Ca-based binders in terms of preventing vascular calcifications, bone abnormalities, and mortality. P removal is about 1800–2700 mg per week with conventional thrice-weekly haemodialysis, but may be increased by using haemodiafiltration or intensified regimens, such as short daily, extended daily or three times weekly nocturnal haemodialysis. Several vitamin D derivatives are currently used for the treatment of secondary hyperparathyroidism. In comparison with the natural form calcitriol, the vitamin D analogue paricalcitol seems to be more fast-acting and less prone to induce hypercalcaemia and hyperphosphataemia, but whether these advantages translate into better clinical outcomes is unknown. Calcimimetics such as cinacalcet can significantly reduce PTH, Ca, and P levels, but they have failed to definitively prove any benefits in terms of mortality and cardiovascular events in dialysis patients. Parathyroidectomy is often indicated in CKD patients with severe persistent hyperparathyroidism, refractory to aggressive medical treatment with vitamin D analogues and/or calcimimetics. This procedure usually leads to rapid improvements in biochemical markers (i.e. significant lowering of serum Ca, P, and PTH) and clinical manifestations (such as pruritus and bone pain); however, the long-term benefits are still unclear.

The advent of recombinant human erythropoietin (epoetin) in the late 1980s transformed the management of renal anaemia, liberating many dialysis patients from lifelong regular blood transfusions, in turn causing severe iron overload and human leucocyte antigen sensitization. Epoetin can be administered either intravenously or subcutaneously, but the half-life of the drug is fairly short at around 6–8 hours, necessitating frequent injections. To circumvent this problem, two manipulations to the erythropoietin molecule were engineered. The first of these was to attach an extra two carbohydrate chains to the therapeutic protein hormone (to make darbepoetin alfa), and the second was to attach a large pegylation chain to make continuous erythropoietin receptor activator. Both of these strategies prolonged the circulating half-life of the erythropoietin analogue. The next erythropoietic agent to be produced was peginesatide, a peptide-based agent which had no structural homology with native or recombinant erythropoietin, but shared the same biological and functional characteristics. Future strategies include stabilization of hypoxia-inducible factor, by orally active inhibitors of the prolyl hydroxylase enzyme, and advanced clinical trials are underway. In the meantime, several large randomized controlled trials have highlighted the potential harm in targeting a near normal haemoglobin of 13–14 g/dL (with an increased risk of cardiovascular complications), and sub-normal correction of anaemia is now advised. Some patients may show mild or severe resistance to erythropoiesis-stimulating agent (ESA) therapy, and common causes include iron insufficiency, infection, and underlying inflammation. Very rarely, patients may produce antibodies against their ESA, which neutralize not only the ESA, but also endogenous erythropoietin, causing pure red cell aplasia.

Voltage dividers provide accelerating voltages to generate multiplier gain. Dynode voltages must remain constant and independent of the light input to maintain stable gain. The standard resistive divider never quite satisfies this requirement, although acceptable performance can be achieved by careful design. The inclusion of zener diodes improves performance but field-effect transistor (FET) circuits can provide gain stability at high mean anode currents, regardless of whether the application is pulsed or analogue. Design procedures for active and semi-active voltage dividers are presented. Dividers based on the Cockcroft–Walton (CW) principle are particularly suited to portable instrumentation because of their low standing current. Consideration is given to pulsed operation, decoupling, switch-on transients, ripple, dynode signals, single cable dividers, and equivalent circuits at high frequencies. Gating is used to protect a photomultiplier, in the presence of high light levels, by reducing the gain electronically. Various methods for gating a voltage divider are presented.

In terms of an analogy to economic markets, the political market for parties has nearly always been an oligopoly. In recent decades, that oligopoly has transformed into a cartel, in which the parties share rather than compete over resources, and effectively conspire to protect their collective interests. The capacity of their leaders to maintain this cartel of parties depends, however, on their ability to control their own parties, giving rise to a new form of party organization, the cartel party. As with all ideal types, there are never any fully fledged cartel parties, just as there were never any fully fledged mass parties or catch-all parties, but the realities of modern politics are better understood as approaches to the cartel party ideal type than as perversions of the catch-all party.

We can’t avoid insects. They scurry past us in the kitchen, pop up in our gardens, or are presented to us in jars by inquisitive children. Despite encountering them on a daily basis, most people don’t know an aphid from an antlion, and identifying an insect using field guides or internet searches can be daunting. Miniature Lives provides a range of simple strategies that people can use to identify and learn more about the insects in their homes and gardens. Featuring a step-by-step, illustrated identification key and detailed illustrations and colour photographs, the book guides the reader through the basics of entomology (the study of insects). Simple explanations, amusing analogies and quirky facts describe where insects live, how they grow and protect themselves, the clues they leave behind and their status as friend or foe in a way that is both interesting and easy to understand. Gardeners, nature lovers, students, teachers, and parents and grandparents of bug-crazed kids will love this comprehensive guide to the marvellous diversity of insects that surrounds us and the miniature lives they lead.

Patients who undergo kidney transplantation have laboratory, bone, and soft tissue abnormalities that characterize chronic kidney disease mineral and bone disorder (CKD-MBD). After successful transplantation, abnormal values of parathyroid hormone, fibroblast growth factor 23, calcium, phosphate, vitamin D sterols, and sex hormones generally improve, but abnormalities often persist. Cardiovascular risk remains high and is influenced by prevalent vascular calcification, and fracture risk increases due to a combination of abnormal bone ‘quality’, compounded by immunosuppressive drugs and reductions in bone mineral density. Patients with well managed CKD-MBD before transplantation generally have a smoother post-transplant course, and it is useful to assess patients soon after transplantation for risk factors relevant to the general population and to patients with CKD. Targeted laboratory assessment, bone densitometry, and X-ray of the spine are useful for guiding therapy to minimize post-transplant effects of CKD-MBD. To reduce fracture risk, general measures include glucocorticoid dose minimization, attaining adequate 25(OH)D levels, and maintaining calcium and phosphate values in the normal range. Calcitriol or its analogues and antiresorptive agents such as bisphosphonates may protect bone from glucocorticoid effects and ongoing hyperparathyroidism, but the efficacy of these therapies to reduce fractures is unproven. Alternate therapies with fewer data include denosumab, strontium ranelate, teriparatide, oestrogen or testosterone hormone replacement therapy, tibolone, selective oestrogen receptor modulators, and cinacalcet. Parathyroidectomy may be necessary, but is generally avoided within the first post-transplant year. A schema is presented in this chapter that aims to minimize harm when allocating therapy.

Collaboration with industry has become the paradigm in public health. Governments commonly develop close relationships with companies that are creating or exacerbating the very problems public health agencies are trying to solve. Nowhere is this more evident than in partnerships with food and soda companies to address obesity and diet-related noncommunicable diseases. The author argues that public-private partnerships and multistakeholder initiatives create webs of influence that undermine the integrity of public health agencies; distort public health research and policy; and reinforce the framing of public health problems and their solutions in ways that are least threatening to the commercial interests of corporate “partners.” We should expect multinational corporations to develop strategies of influence. But public bodies need to develop counter-strategies to insulate themselves from corporate influence in all its forms. The author reviews the ways in which we regulate public-public interactions (separation of powers) and private-private interactions (antitrust and competition laws), and argues for an analogous set of norms to govern public-private interactions. The book also offers a novel framework that is designed to help public bodies identify the systemic ethical implications of their existing or proposed relationships with industry actors. The book makes a compelling case that, in public health, the paradigm public-private interaction should be at arm’s length: separation, not collaboration. The author calls for a new paradigm to protect and promote public health while avoiding the ethical perils of partnership with industry.

Though the Renaissance map—made newly accurate and newly ubiquitous by the Cartographic Revolution—delighted, inspired, and fascinated, it also unsettled, upset, and disturbed sixteenth- and seventeenth-century readers. Early Modern English Literature and the Poetics of Cartographic Anxiety is the first monograph to demonstrate how early modern anxieties about maps and map logics accompanied an early modern poetics of representational crisis. The book first considers the manifold ways that the cartographic provoked suspicion, unease, and even hostility in early modern Britain, and it highlights literature’s sensitivity to the map’s representational deceptions and politically menacing implications. Second, it explores how Renaissance English literature, and specifically epic poetry, mounted a sustained critique of cartographic materials, of their strategies of representation, and of their often realpolitik, strategically distortive uses. In considering the ways epic poetry channels anxieties about cartographic technologies into a critique of early modern literature’s own protocols of representation, the bookpursues an early modern poetics of anxiety, one that productively complicates concepts of allegory, description, personification, bibliographic materiality, narrative, temporality, analogy and other elements of literary representation. Early Modern English Literature and the Poetics of Cartographic Anxiety reads three major poems of the period—Spenser’s The Faerie Queene (1590, 1596), Drayton’s Poly-Olbion (1612, 1622), and Milton’s Paradise Lost (1667, 1674)—in terms of their vexed and vexing relationships with cartographic materials, and shows how the productive protest staged by these texts inflects early modern and contemporary accounts of representation itself.

The relationship between low birth weight (LBW) and subsequent increased risk of hypertension and renal disease in humans is now well established. The initial hypothesis suggested that an adverse intrauterine environment, reflected by LBW, would impact renal development, resulting in a low nephron number and predisposition to hypertension and renal disease. Studies in various populations have shown a direct correlation between birth weight and nephron number, and in infants, nephron numbers are reduced in those of LBW. Among Caucasian and Australian Aboriginal adults, lower nephron numbers are associated with higher blood pressure, whereas higher nephron numbers appear to protect against hypertension. LBW is currently the best clinical surrogate for low nephron number and has been independently associated with higher blood pressure from infancy through to adulthood in many populations, as well as an increased risk of proteinuria, reduced glomerular filtration rate, chronic kidney disease, and end-stage renal disease in later life. The pathophysiology is analogous to that in other chronic kidney diseases where surviving nephrons are subject to hyperfiltration early on, resulting in glomerular hypertrophy, proteinuria, and eventually, especially in the setting of other renal disease risk factors, glomerulosclerosis, and loss of renal function. Mean nephron number varies by up to 13-fold in certain populations, however, therefore nephron number is unlikely the sole developmentally programmed risk factor for renal disease in later life, but may be a first ‘hit’ impacting an individual’s susceptibility to or resistance to superimposed renal injury. Augmentation of nephron number perinatally has only been addressed in experimental settings. In humans, therefore optimization of nephron number is likely best achieved through good perinatal care and adequate postnatal nutrition. Cardiovascular disease and diabetes are also developmentally programmed and therefore likely coexist in subjects with LBW and low nephron numbers. Awareness of an individual’s birth weight should serve to highlight the possibility of low nephron number and potential risk for future hypertension and renal disease, which may be attenuated by optimization of early nutrition, lifestyle choices, and management of other risk factors for renal disease.