Cellular Conclusion

To obtain an increased intrinsic capacity to transgress biological membranes, a number of different modifications have been introduced to PNA. These modifications include conjugation of PNA to Hpophilic moieties [51, 97, 98], conjugation of PNA to certain so-caUed ceU-penetrating peptides [49, 55, 56, 66, 99-102] and conjugation to different moieties, which are supposed to be internahzed by specific cellular receptors [48, 103-105]. The work on cellular dehvery of PNA is, like the related work on ex vivo and in vivo effects of PNA, very difficult to summarize conclusively. First of all, the pronounced diversity of the reporter systems employed makes it impossible to directly compare the studies. Secondly, the widespread use of fluorescence studies in spite of the many inherent pitfalls of this technique makes it sometimes difficult to judge even qualitatively whether a presented result actually indicates cellular uptake. We have recently published a comprehensive review on cellular dehvery of PNA [82], with a more detailed assessment of the PNA dehvery hterature. 

While the ECG is an invaluable tool for the observation of heart rate and rhythm, as well as for the diagnosis of conduction abnormalities, ischaemia, and infarcts, its detailed interpretation is not without pitfalls. One reason for this is that different changes in cardiac cellular behaviour may give rise to very similar effects on the ECG. This makes it difficult to draw conclusions from a patient s ECG to the underlying (sub-)cellular mechanisms. This issue is usually referred to as the inverse problem. ... 

Allelopathic inhibition of mineral uptake results from alteration of cellular membrane functions in plant roots. Evidence that allelochemicals alter mineral absorption comes from studies showing changes in mineral concentration in plants that were grown in association with other plants, with debris from other plants, with leachates from other plants, or with specific allelochemicals. More conclusive experiments have shown that specific allelochemicals (phenolic acids and flavonoids) inhibit mineral absorption by excised plant roots. The physiological mechanism of action of these allelochemicals involves the disruption of normal membrane functions in plant cells. These allelochemicals can depolarize the electrical potential difference across membranes, a primary driving force for active absorption of mineral ions. Allelochemicals can also decrease the ATP content of cells by inhibiting electron transport and oxidative phosphorylation, which are two functions of mitochondrial membranes. In addition, allelochemicals can alter the permeability of membranes to mineral ions. Thus, lipophilic allelochemicals can alter mineral absorption by several mechanisms as the chemicals partition into or move through cellular membranes. Which mechanism predominates may depend upon the particular allelochemical, its concentration, and environmental conditions (especially pH). 

Monod J, Jacob F. General conclusions teleonimic mechanisms in cellular metabolism, growth and differentiation. Cold Spring Harbor Symp Quant Biol 1961 26 389-401. 

In conclusion, Eqs. (140) and (141) are applicable to quantify not only the transmonolayer kinetics of highly membrane interactive permeants, but also the kinetics of less membrane interactive compounds. Notably, the examples emphasize the importance of simultaneously measuring the disappearance of a compound from the donor solution and its appearance in the receiver and demonstrate how interactions with proteins on either side of the cellular barrier influence permeability. 

Electron microscopic evaluation of infected Caco-2 monolayers grown on membranes, under conditions that induced cellular polarization, prompted the conclusion that the larvae occupy the cytoplasm of cells they invade (ManWarren et al., 1997). Apical and basal plasma membranes appeared to be preserved in infected cells (Fig. 6.3). These findings reproduced the observations of Wright (1979) in his examination of intestinal tissues from infected mice. In contrast, when Li et al. (1998) performed similar experiments in HT29 monolayers grown on plastic, they concluded... 

Many striking similarities have been noted in the cellular processes of different organisms. Consequently, analogies are used (unless conclusive, contrary evidence is available), in order to account for a biological reaction known to occur, for example, in a plant, and believed to take place in other organisms. 

While the conditional gene knockout experiments are supportive of a role for the NMDA receptors in memory, they are less than fully conclusive in linking the synaptic coincidence-detection feature of the NMDA receptor to memory formation. Like all loss-of-function studies, CA1-specific gene-knockout experiments could, in theory, produce memory impairment via a mechanism independent of the coincidence-detection function of the NMDA receptor. For example, one may argue that the physical absence of the NMDA receptor channels may cause subtle structural reconfiguration at the synapse, thereby altering normal synaptic transmission. Therefore, the memory impairment in CA1-specific NR1 knockout mice does not allow a firm conclusion that the coincidence-detection function of NMDA receptors controls learning and memory processes at the cellular level. 

Several inorganic arsenic compounds are weak inducers of chromosomal aberrations, sister chromatid exchange, and in vitro transformation of mammalian and piscine cells. However, there is no conclusive evidence that arsenic causes point mutations in any cellular system (Pershagen and Valuer 1979 Belton et al. 1985 Lee et al. 1985 Deknudt et al. 1986 Manna and Mukheijee 1989). Studies with bacteria suggest that arsenite is a comutagen, or may inhibit DNA repair (Belton et al. 1985). 

The choice of iron chelators on the basis of both molecular and cellular criteria was discussed in 2003 (374). One 2005 review is concerned with the design of orally active iron chelators (375), another considers the prospects for effective clinical use of several hydro-x5rpyridinones, dealing with novel species such as the 1-allyl compound as well as with the established deferiprone (LI) and desferrioxamine (Desferal, DFO) (376). A review dated 2006 deals with relevance of iron mobilization from both transferrin and other iron-containing proteins by LI to the treatment of various anemias and other iron-overload conditions (377). Two 2007 reviews concentrate on LI, as the only hydroxypyridinone in general clinical use. One author concludes that, on balance, LI is to be preferred to DFO. This conclusion is on the grounds that, despite the not infrequent occurrence of minor side effects, the incidence of serious side effects... 

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