Physiological buffer

Chemical self preservation, p. 74 Drugs by design and discovery, p. 96 Drug delivery, p. 344 Physiological buffers, p. 453... 

Buffers resist a change in pH when protons are produced or consumed. Maximum buffering capacity occurs 1 pH unit on either side of pAl,. Physiologic buffers include bicarbonate, orthophosphate, and proteins. 

The water-soluble compound 36b, very stable within a physiological buffer at 37 ° C, exhibits cytotoxic effects on ovarian A2780 human cancer cells and promotes apoptosis to a greater extent than platinum drugs [103]. 

BSS with the addition of glutathione (oxidized) and dextrose as energy sources, bicarbonate as a physiological buffer, and a phosphate buffer system to maintain the products storage pH in the physiological range [296,297],... 

Physiological Buffer Systems Recently, a lot of efforts have been made on how to increase the biorelevance of the Caco-2 model [63, 47, 64, 65,105], Historically, the media used for Caco-2 experiments were buffered at pH 7.4 on both sides of the monolayer. The pH in the cellular interstice and blood compartment is known to be 7.4. However, the pH in the upper GI tract under fasted conditions ranges from 5.0 to 6.5, with an acidic microclimate existing just above the epithelial cell layer estimated to be between 5.8 and 6.3 [90], The pH of the apical medium can have a critical effect on the transport of drugs, especially for drugs with a pKa close to 7, or when pH-dependent transporters are involved. 

The PMR spectrum of protein SI suggests that the protein has considerable tertiary structure in physiological buffer and is more flexible than normal globular proteins of its molecular weight (Moore and Laughrea, 1979). No difference was observed when the protein was prepared in the presence or absence of urea at neutral pH. The spectra obtained in this study resemble those previously obtained with salt-extracted SI by Little-child and Malcolm (1978). 

When urea-denatured preparations of protein Lll are introduced into physiological buffers, two different conformations occur as shown by NMR studies (Kime et al., 1980). One form is distinctly folded while... 

The superfusion of isolated nerve terminals ( synaptosomes ) is a widely used technique for interrogating the pharmacological properties of presynaptic receptors and their biochemical mechanisms. Physiological buffer continuously flows over a layer of synaptosomes loaded with radiolabelled transmitter, such that released transmitter is removed in the perfusate and collected. A key feature of this methodology is that it eliminates transmitter crosstalk between different boutons, enabling presynaptic events to be studied in isolation (Raiteri and Raiteri 2000). 

The most convincing proposal is that camosine plays one or more roles in control of intracellular hydrogen ion concentration (Abe, 2000 Vaughan-Jones et al, 2006). Camosine is an effective physiological buffer it is presumed that this property explains its predominant association with white, glycolytic, muscles which possess relatively few mitochondria and thereby generate lactic acid. Not only may camosine, also possible in its acetylated form, help to directly suppress the rise in hydrogen ion concentration but its ability to activate the enzyme carbonic anhydrase (Temperini et al, 2005) would increase bicarbonate buffer capacity. These properties may help explain camosine s protective action in ischaemia, a condition associated with severe intracellular acidosis. 

In athletes involved in explosive/in tense muscle exercise, it is likely that the raised camosine levels are required as physiological buffers. Hence it is possible that raising camosine levels may improve muscle performance by increasing buffer capacity. In an attempt to increase camosine levels by dietary means, but circumventing the effects of serum camosinase, increasing p-alanine intake has been investigated... 

Use whole cells for metabolism studies. This avoids the use of non-physiological buffer and cofactor compositions. 

The better correlation with in vitro data obtained from hepatocytes (relative to microsomes) deserves further investigation. This difference may be due to a difference in catalytic activity in vivo relative to optimal conditions in vitro. It is possible that use of non-physiological buffer conditions will overstate or understate the contribution of a particular P450 to overall metabolism. For example, the role of cytochrome bs/OR in catalytic activity is influenced by ionic strength (Schenkman et al., 1994 Voznesensky and Schenkman, 1994) which is a variable in microsmal incubations but not in the intracellular space of a hepatocyte. This suggests that performing incubations of cDNA-expressed enzymes under conditions which mimic intact cells may substantially improve correlations. 

Carbonic acid, H2CO3, is a weak acid that dissociates by the above reaction (B). In general, a solution of a weak acid HA that dissociates into H and A will serves as a buffer solution. Thus, respiration in lungs contributes to physiological buffer actions. 

In many of the experiments to be described, buffers were used to stabilize the pH of the system, obviating the need for large bath volumes or pH-stat. It was assumed initially that buffering would have only secondary effects on our measurements. As will be seen, however, the nature of the buffer can have profound effects on both swelling equilibria and kinetics. This result is important for any ionizable gel system that one expects to use for therapeutic purposes, since such systems will either be stored in pH-buffers, or encounter physiologic buffering when placed in contact with body fluids. 

A sourdough yeast strain (S. cerevisiae) and two bacterial species (S. marcescens, B. subtilis) were treated in a physiological buffer (PBS).The first experiments (with the yeast) were performed in a batch apparatus (Fig. 10) as well as in a semi-continuous apparatus (Fig. 12). As the latter device showed a higher efficiency in the microbial inactivation than the... 

Zhang Y, Wilson GS. Electrochemical oxidation of hydrogen peroxide on platinum and platinum/iridium electrodes in physiological buffer and its applicability to hydrogen peroxide-based biosensors. Journal of Electroanalytical Chemistry 1993, 345, 253-271. 

P. K. Janicki, W. A. R. Erskine, and M. F. M. Jones, HPLC method for the direct determination of the volatile anaethetics halothane isoflurane, and enflurane in water and in physiological buffer, J. Chromatogr., 518 250 (1990). 

Size-exclusion HPLC is particularity useful in either direct pharmacodynamic studies of the radiolabeled product or indirect studies that employ a labeled monoclonal antibody. In order to observe shifts in apparent MW due to noncovalent binding interactions, the mobile phase for these analyses should be a physiological buffer and the ligand size cannot be less than half that of the labeled protein. In cases where complexation may interfer with in vivo targeting, size-exclusion HPLC can be used prior to clinical administration of the potential or existing biotechnology product to establish the most effective regimen or dose. 

Unger, S.H., Chiang, G.H. (1981) Octanol-physiological buffer distribution coefficients of lipophilic amines by reversed-phase high-performance liquid chromatography and their correlation with biological activity. J. Med. Chem. 24(3), 262-270. 

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