Points of Concern

Although there is no doubt that TAC is a good measure of total content of antioxidants in food and beverages, it cannot say anything about the bioavailability of these compounds. More important from a clinical point of view is the question of whether TAC can be a valid biomarker of the antioxidant status of the body. 

A considerable variation of TAC values of blood plasma (and other body fluids) for healthy persons can be seen from data reported by various authors (Table 8). One reason for these discrepancies is the diversity of assay methods employing different oxidants (in the inhibition assays) and indicators. There may be additional reasons for these discrepancies. Due to differences in reactivities of the 

Antioxidant activity may also be a nonlinear function of concentration of some antioxidants, that is, TAC values may decrease with increasing concentration of the compound studied (M21, W7). In some methods TAC was reported to be not proportional to the dilution (or volume introduced) of blood plasma (C9, S8, W6). This effect may be due to binding of ABTS + (and other indicators) to plasma proteins, especially albumin (M17), or binding of some sample components to indicator proteins (04) Therefore, analysis of the same volume of the fluids studied can be recommended nevertheless, comparison of results obtained under different conditions can hardly be done in some cases. 

How well do the results of TAC determinations by different methods coincide One group found no correlation between results by ORAC and TEAC and by FRAP and TEAC and only a weak correlation between ORAC and FRAP (r = 0.35, 

Is TAC, representing mainly the second line of antioxidant defense (interception of reaction of uncontrolled oxidation), as important as specific antioxidant mechanisms of the first line of antioxidant defense (preventing the formation of reactive oxygen species) If so, one should perhaps expect high TAC values of biological fluids of crucial importance such as seminal plasma. Instead, TAC of blood plasma and seminal plasma is comparable with that of urine and much lower than that of feces (Tables 8 and 10). 

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Tray efficiency is as high as for bubble caps and almost as high as sieve trays. It is higher than bubble caps in some systems. Performance indicates a close similarity to sieve trays, since the mechanism of bubble formation is almost identical. The real point of concern is that the efficiency falls off quickly as the flow rate of vapor through the holes is reduced close to the minimum values represented by the dump point, or point of plate initial activation. Efficiency increases as the tray spacing increases for a given throughput. 

Winter operation—In order not to allow the water velocity in the tubes to fall below 3 ft/sec in the winter, you may have to compromise with the selected unit as based on 90°F water. If the average four-month winter temperature drops to 70°F, the quantity of water required will be reduced as will the velocity through the tubes. The low velocity is the point of concern. Check to determine the prevailing conditions. 

Fast deflagration—the flame position is much closer to the precursor shock wave. Overdriven detonation—a transition to detonation that has just occurred and the detonation is significantly overdriven with the peak pressure, well in excess (2-3 times) of the value usually associated with a steady Chapman-Jouget (CJ) detonation. This peak pressure generated during the transition process is a particular point of concern in the industry. 

While not officially required, the FDA does have the authority to request, on a case-by-case basis, specific tests it feels may be necessary to address a point of concern. A genetic toxicity test could be part of such a request. In general, therefore, companies deal with genetic toxicity (after screening ) on a case-by-case basis, dictated by good science. If more than a single administration is intended, common practice is to perform the tests prior to submitting an IND. 

One additional point of concern in the extension of the PHPMS technique to elevated pressures is that the criteria normally considered to be necessary for accurate aperture sampling of a high-pressure ion source will probably be violated. A condition of molecular flow through the aperture is generally required for accurate sampling. Molecular flow occurs when the critical dimension (such as the diameter of an orifice or the width of an exit slit) is equal to or smaller than the... 

A first point of concern is the knowledge of the pH domain where the molecule under scrutiny is stable. For these classical POMs, such domains were determined and found to he shifted to more alkaline pH values as the number of added electrons increases [19-23]. H4SiWi2O40, H3PW12O40, and H6P2W18O62 are known as strong adds in aqueous solutions, presumably with a uniform acidity [29]. In addition, each reduction step increases the negative charge density on the... 

B. Besides the reproductive effect observed in the key study, are there other health end-points of concern What are the significant data gaps ... 

Chapter 5 includes highlights of topics of importance in the formulation of liquid products. However, this chapter is not an all-inclusive guide to formulation. Only highlights of points of concern are presented here, and the formulator is referred to several excellent treatises available on the subject. 

Several synthetic methods are now available for the preparation of mixed-metal clusters.1 However, when particular clusters are desired, two main points of concern for their synthesis often remain the availability and price of the precursors, and the yield of the reaction. Mixed-metal clusters containing ruthenium have attracted considerable interest mainly because of the variety of structural and bonding types encountered, and of their potential for homogeneous and heterogeneous catalysis.2... 

For an effective synthesis of trichodermol, there remain three points of concern. First, the formation of an equimolar mixture of diastereomers (97) leads to inefficiency, since realistically only half of the material can be used. Second, the ester group of complex (168) has to be reduced to methyl, a multistep operation which again is unattractive it would be better to attach to complex (30) an enolate having methyl in place of the ester. Third, the introduction of the trichodermol 4-hydroxy group must be accomplished in some manner. 

To date, the challenges associated with development of an oral MR dosage form for water-insoluble drugs have not been systematically studied and discussed. In many cases, the physicochemical properties of the drug and its sensitivity to the conditions of the Gl track make it more difL cult to attain the desired absorption and PK proLle. This is a clear point of concern in developing a MR product for poorly water-soluble drugs. 

A point of concern is that for the same PAQM values sometimes big deviations in subjective scores are found (see Fig. 1.9). 2... 

Acknowledgements. A point of concern to us is incorrect bibliographic citations in this paper every citation has been checked against the original article, or in a very few cases, Chemical Abstracts. The author is indebted to Kirsten Krause for this service and for considerable other support during this undertaking. Professor Michael J. Clarke, the editor, is to be thanked for his efforts in polishing the manuscript. Many thanks are also due to Sandy Rivard who patiently typed all of the tables, in spite of my many revisions. 

Because of the problems of relieving cryogenic fluids, many points of concern need to be verified before a valve is installed on an LNG application. So far the best way to do that is to test the valve under cryogenic conditions. Currently there are two main tests used. 

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