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An alternate approach would be to isolate progenitor cells Realistically discount 40mg zocor with amex cholesterol chart mmol/l, it is hard to imagine exogenous cells to functionally from the retina itself and use these cells for transplantation pur- replace inner or outer hair cells generic 10mg zocor free shipping vldl cholesterol definition. Indeed, it has been shown that when transplanted to the would be the spiral ganglion neurons, which are less-strictly diseased adult retina, these progenitor cells express both an organised. In addition to replacing the neurons per se, implanted integrative plasticity and the capacity to differentiate into reti- exogenous cells could function as an intermediate cellular ābuild- nal neurons and photoreceptors (22). This chapter will outline the rationale host cells, and thus halt or slow down an ongoing degenerative underlying recent efforts to make use of cell and tissue trans- process. There is ample evidence that exogenously adminis- plantation for treating the injured inner ear. It should be noted tered substances such as neurotrophic factors and antioxidants already here that inner ear transplantation is still at an early can prevent inner ear injuries and stop the progress of degener- experimental level and thus very far from being a clinical tool. The idea would be to introduce cells into Irrespective of whether tissue transplantation will be imple- the cochlea that could release, for example, neurotrophic fac- mented in clinical practice, the efforts are revealing valuable tors needed to maintain viable spiral ganglion neurons or hair fundamental principles. The requirements for the ļ¬nal location of the implanted our own laboratory (24), illustrating the approaches used so far cells within the cochlea would be much less precise and there will be discussed, as well as the future steps that need to be would be no need for the cells to form functional contacts with taken to fully prove the concept. Moreover, by genetically modifying the cells, theoretically any biological substance could be released. Although the focus of present research, as well as of this chap- ter, is on replacement therapies, efforts to augment auditory Transplantation rationale function will most likely increase in the near future. Not only is there a clinical urgency to ļ¬nd cures against progressive hearing The aim of tissue transplantation into the inner ear, as loss, e. This approach, also using bone marrow cells, has been applied to If a cell replacement therapy aiming at introducing exoge- the inner ear with positive results (26). An alternative is to use nous cells to replace missing spiral ganglion cells should ever be tissue from another individual of the same species, allografting. What are the possible transplantation sites in the inner is important to ļ¬nd donors as close to the recipient as possible to ear? Will immature cell types differentiate into function- antigens are formed by the major histocompatibility complex ally appropriate cochlear cells? The eye and some other tissues such as the Donor tissue brain are considered to be immunologically privileged sites where the immune system activity is very much reduced. The There are several cell types that could be used for transplanta- inner ear, however, is not an immune-privileged site as once tion into the inner ear. For clinical applications where human tissue is explored are embryonic and adult stem cells, embryonic neural not readily available, e. Moreover, modern the possible exception of autografting, transplantation often molecular tools make it feasible to further design the donor cells. As with all transplantations, there is a potential risk of an adverse immune response against the grafted tissueāa host-versus-graft reactionāleading to transplant Stem cells rejection. Most advantageous would be the use of cells from the individual (the recipient or host) itself, so-called autografting A stem cell is characterised by its capacity to self-renew and (Fig. An autologous approach, which essentially elimi- give rise to a wide range of different cell types. There has been a massive focus on stem cells due to their potential to replace degenerated cells, both for endogenous cell regenera- tion and for therapeutic purposes (28ā30). Two principally different types of stem cells are considered for transplantation into the inner ear, embryonic stem cells, and adult stem cells. However, within each group, there are numerous types of stem cells, each with its speciļ¬c origin and lineage commitment, survival capability, etc. Embryonic stem cells are obtained from a very early stage of embryological development, from the inner cell mass of the blas- tocyst. These cells are especially interesting as transplantation candidates as they are both very proliferative and totipotent, i. Their capacity to deļ¬ned as transplanting tissue from individuals of the same species while xenografting involves a donor from another species, e. In give rise to new cell types can be demonstrated by injecting both cases, immmunosuppression is often required to limit host-versus-graft embryonic stem cells into immunodeļ¬cient mice, resulting in reactions. Tissue can also be obtained from and transplanted to the same the formation of benign teratomas containing cells of all three individual, autografting. If embryonic stem cells can be made to differentiate 292 The future into true spiral ganglion cells, it would create a nearly unlimited experimental models. Also adult human spiral ganglion cells source of transplantable cells for inner ear treatment.
When one is on a ship which is moved by the sea and looks at the land buy discount zocor 40 mg on-line cholesterol crystal definition, it is as if the land moves (460 b 26ā7) best zocor 10mg cholesterol levels chart nz. Weak stimuli of pleasure and pain are extruded by stronger ones and escape our attention (461 a 1ā3). Dreams occur in a later stage of sleep; they are often distorted and unclear, but sometimes they are strong (461 a 18ā27). Melancholics, drunk people and those suffering from fever have confused and monstrous dream images (461 a 21ā2). When one presses a ļ¬nger under oneās eye, one single object appears double (462 a 1). Sometimes, during sleep, one is aware of the fact that one is dreaming (462 a 2ā8). At the moment of falling asleep and of awakening, one often sees images (462 a 10ā11). Young people see in the dark all kinds of appearances when their eyes are wide open (462 a 12ā15). In situations of half-sleep, one can have weak perceptions of light and sounds from oneās environment (462 a 19ā25). Many people never had a dream in their whole lives; others ļ¬rst got them after considerable advance in age (464 b 1ā11;cf. This is a substantial list of empirical claims, some of which testify to Aris- totleās sharp observational capacities (for example, nos. However, we also ļ¬nd claims that are highly questionable from a modern point of view or for which the empirical basis can only be said to be very weak (e. It is difļ¬cult to decide to what extent these ādataā (phainomena or sumbainonta, as Aristotle would call them) are derived from deliberate and purposeful observation by Aristotle and his pupils themselves, or just from common human experience (on the list, observations 15 and 25 are also found in other biological works of Aristotle, but they are evidently only a minority). Moreover, we should certainly take into account the pos- sibility that Aristotle has borrowed some of these data from other scientiļ¬c writings, for example the psychological works of Democritus (whom Aris- totle mentions in Div. However, since this tradition has only been preserved in fragments, it is difļ¬cult to assess the extent of his dependence on earlier sources. Yet when looking more closely at the way in which these empirical ādataā are used in Aristotleās argument in On Dreams, it becomes clear that the treatise goes far beyond the level of empirical fact-ļ¬nding. Aristotle does not present his theory as being built up, so to speak, inductively on the basis of a number of observations; on the contrary, the three research questions mentioned above ((i), (ii) and (iii)) are treated in a systematical and deductive way, and empirical ādataā are mentioned in the course of this theoretical argument ā often in the form of examples or analogies ā in order to support or clarify opinions and presuppositions which Aristotle already seems to take for granted. And although Aristotleās style of reasoning seems very cautious and essayistic ā the ļ¬rst chapter, for example, is highly aporetic25 ā it is, in fact, rather dogmatic. The general impression one gets is that empirical evidence is primarily mentioned when it suits the argument ā and if not, it is either ignored or explained away in a questionable manner. Thus at the end of On Dreams, it turns out that the three questions raised at the beginning are to be answered as follows: (i) Dreams belong to the sensitive part of the soul qua imaginative part (459 a 21); dreaming is not an operation of sense-perception but of āimag- inationā, which is deļ¬ned by Aristotle as āthe movement which occurs as a result of actual perceptionā (459 a 17ā18). This deļ¬nition, together with Aristotleās use of the words phantasia, phantasma, and phainesthai,isin broad agreement with his general theory of āimaginationā in On the Soul, to which he explicitly refers (459 a 15). In the course of the long argument which leads to this conclusion, only claims (1) and (2) play a part; for the rest, the argument is purely theoretical and logical. Aristotle assumes the following mechanism: During the waking state, the sense-organs are stimulated by a great quantity of sense-movements (stimuli brought about by sensible objects); but not all of these movements are equally strong. The stronger movements overrule the weaker, so that the weaker are ānot noticedā by the perceiving subject (460 b 28ā461 a 8). Aristotle assumes, however, that the remnants of these weaker movements remain present in the sense-organs in the form of traces. When in sleep the sense-organs have stopped being active ā and as a result of this cannot receive new stimuli ā the remnants of 25 For an analysis see van der Eijk (1994) 36ā8. Aristotle on sleep and dreams 183 these weaker movements, which escaped our attention in the waking state, get, so to speak, a second chance to āpresent themselvesā to the perceiving subject. The physiological picture to be drawn for this process is not completely clear, but seems to be roughly as follows. Aristotle thinks that apart from the peripheral sense-organs (eyes, ears, nose, etc. His view seems to be that, normally speaking, a sensitive impulse is transmitted from the peripheral sense-organs to the heart, where it is received, recorded and noticed, and co-ordinated with movements from other senses (461 a 31). The transmitting agency is probably the blood (although this is not quite clear from the text). The āperceptionā or ānoticingā of these movements is dreaming in the strict sense.
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