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Immunoglobulin therapy in the 21st century: the dark side of the moon

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197033 Year: Pages: 124 DOI: 10.3389/978-2-88919-703-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-08-16 10:34:25
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In the early decades since the introduction in the early '80s of immunoglobulin therapy many studies tried to identify which clinical indications might benefit from the therapy, which treatment’s schedules are effective and safe. It is universally accepted that immunoglobulin therapy is a life-saving treatment in patients with PID. The rise of new indications for further different clinical conditions resulted in a steady increase in demand for immunoglobulins. Currently the consumption of immunoglobulin for PID represents a small fraction of the market. In the recent past we have been observing:1) An increase in the demand for plasma and in the consequent need to increase the number of donors;2) Changes in methods to improve IgG recovery and to increase productivity as a response to growing clinical demand;3) Introduction of immunoglobulin treatments with higher concentration;4) Changes in the timing of administration with an increase in the rate of infusion;5) Introduction of immunoglobulin treatment administered subcutaneously mainly confined initially to patients with PID and later extended to other clinical indications which often require higher volumes of infusion. Doctors following patients with PID were initially alarmed only to a possible risk of shortage. More relevant and less discussed appear the possible consequences of:1) the risk of an improper transfer of information on treatments from a clinical indication to another. In particular, the idea of a mere replacement function in patients with PID might possibly be borrowed from the model of other clinical conditions requiring a replacement such as haemophilia. In PID, immunoglobulin treatment instead is obviously replacing a missing feature. However, other immune alterations are responsible for the large number of PID-associated diseases including inflammatory manifestations and tumors, common causes of morbidity and mortality. The immunomodulatory effects of immunoglobulin administered at replacement dosages on multiple cells and immune system functions are still largely to be checked in in vitro studies and in vivo.2) the changes in the immunoglobulin production and schedules of administration. These should have been assessed in studies of drug surveillance, necessary in order to evaluate on large numbers of what it is initially reported on patients enrolled in the pivotal clinical trials, usually in the absence of most of the main disease-associated clinical conditions affecting pharmacokinetics, efficacy and tolerability. Severe side effects are now more frequently reported. This requires surveillance studies in order to verify the tolerability. Nowadays, personalized health research presents methodologic challenges, since emphasis is placed on the individual response rather than on the population. Even within a universally accepted indication, such as in PID, the identification of prognostic markers should guide the therapeutic intervention.3) the risk of a decrease in the surveillance and monitoring of PID-associated clinical conditions. In fact, self- administration of immunoglobulins administered subcutaneously increased the independence of a number of patients. On the other hand, it led to the reduction in the number of contacts between specialized centers and patients who often require a close monitoring of disease-associated conditions. A wide debate between experts is necessary to afford the new challenge on immunoglobulin usage.

Habituation mechanisms and their impact on cognitive function

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194629 Year: Pages: 110 DOI: 10.3389/978-2-88919-462-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Habituation describes the progressive decrease of the amplitude or frequency of a motor response to repeated sensory stimulation that is not caused by sensory receptor adaptation or motor fatigue. Habituation can occur in different time scales: habituation within a testing session has been termed short-term habituation, whereas habituation across testing sessions has been termed long-term habituation. Generally, the more spaced the stimuli for inducing habituation are presented (i.e. the slower habituation is induced), the longer it seems to take to recover the behavioural response to its initial magnitude. Habituation is opposed by behavioural sensitization, which is thought to be an independent mechanism that leads to an increased behavioural response, especially if the sensory stimulus is annoying or aversive. Habituation provides an important mechanism for filtering sensory information, as it allows filtering out irrelevant stimuli and thereby focussing on important stimuli, a prerequisite for many cognitive tasks. The importance is demonstrated in mental disorders that are associated with disruptions in habituation, e.g. schizophrenia and autism spectrum disorders. The inability to filter out irrelevant information in patients with these disorders strongly correlates with disruptions in higher cognitive functions, such as in different types of memory and attention. Habituation is also considered to be the most basic form of non-associative implicit learning, and it can be observed throughout the animal kingdom. Based on the importance of habituation for cognitive function and therefore for the survival of an animal, it is assumed that habituation mechanisms are highly conserved across species. On the other hand, there is emerging evidence for a multitude of homo- and heterosynaptic mechanisms underlying habituation, depending on the modality of sensory stimulation, the level of sensory information processing where habituation occurs, and the temporal composition of sensory stimulation. Eric Kandel used the sea hare Aplysia in order to study habituation mechanisms of the gill withdrawal reflex; however, the molecular mechanisms remain largely elusive to date. A multitude of different organisms, behaviours, and experimental approaches have been used since in order to study habituation, but still surprisingly little is known about the underlying mechanisms. New insights also come from an unexpected side: in the recent past, groups that have been studying molecular mechanisms underlying short- and long-term synaptic plasticity phenomenons in different parts of the rodent brain are starting to link these plasticity processes to behavioural habituation. The scope of this Frontier Research Topic is to give an overview over the concept of habituation, different animal and behavioural models used for studying habituation mechanisms, as well as the different synaptic and molecular processes suggested to play a role in behavioural habituation through Original Research Articles, Methods, Hypothesis & Theory Articles, and Reviews.

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