Inactivation incomplete

Fig. 1. An amplified outline scheme of the making of various wiaes, alternative products, by-products, and associated wastes (23). Ovals = raw materials, sources rectangles = wines hexagon = alternative products (decreasing wine yield) diamond = wastes. To avoid some complexities, eg, all the wine vinegar and all carbonic maceration are indicated as red. This is usual, but not necessarily tme. Similarly, malolactic fermentation is desired in some white wines. FW = finished wine and always involves clarification and stabilization, as in 8, 11, 12, 13, 14, 15, 33, 34, followed by 39, 41, 42. It may or may not include maturation (38) or botde age (40), as indicated for usual styles. Stillage and lees may be treated to recover potassium bitartrate as a by-product. Pomace may also yield red pigment, seed oil, seed tannin, and wine spidts as by-products. Sweet wines are the result of either arresting fermentation at an incomplete stage (by fortification, refrigeration, or other means of yeast inactivation) or addition of juice or concentrate.

Figure 4. Effects of dihydro-brevetoxin B (H2BVTX-B) on Na currents in crayfish axon under voltage-clamp. (A) A family of Na currents in control solution each trace shows the current kinetics responding to a step depolarization (ranging from -90 to -I-100 mV in 10 mV increments). Incomplete inactivation at large depolarizations is normal in this preparation. (B) Na currents after internal perfusion with H2BVTX-B (1.2 a M). inactivation is slower and less complete than in the control, and the current amplitudes are reduced. (C) A plot of current amplitudes at their peak value (Ip o, o) and at steady-state (I A, A for long depolarizations) shows that toxin-mOdified channels (filled symbols) activate at more negative membrane potentials and correspond to a reduced peak Na conductance of the axon (Reproduced with permission from Ref. 31. Copyright 1984 American Society for Pharmacology and Experimental Therapeutics).

Viral vaccines present problems of safety testing far more complex than those experienced with bacterial vaccines. With killed viral vaccines the potential hazards are those due to incomplete virus inactivation and the consequent presence of residual live virus in the preparation. The tests used to detect such live virus consist of the inoculation of susceptible tissue cultures and of susceptible animals. The cultures are examined for cytopathic effects and the animals for symptoms of disease and histological evidence of infection at autopsy. This test is of particular importance in inactivated poliomyelitis vaccine, the vaccine being injected intraspinally into monkeys. At autopsy, sections of brain and spinal cord are examined microscopically for the histological lesions indicative of proliferating poliovirus. 

A failure by one of us to take fully into account the presence of inactivated xanthine oxidase, leading to misinterpretation of incomplete reaction of enzyme with iodoacetamide and hence to the apparently erroneous conclusion, that the two FAD molecules in the enzyme were non-equivalent (72), may serve as a warning to others. This reagent has since been shown to alkylate the flavin of reduced xanthine oxidase molecules, whether these are of the active or inactivated forms (73). Thus, under conditions where little of the inactivated form is reduced, the reagent becomes a specific one for the active enzyme (20). In the original experiments (59, 72) the content of active enzyme was, by coincidence, rather close to half of the total enzyme present. Thus, the presence of inactivated enzyme, rather than a lack of reactivity of one... 

X inactivation occurs early in the female embryo and is random, fixed, and incomplete. In a cell, all X chromosomes but one are inactivated. 

X-inactivation is incomplete—there are regions throughout the X chromosome, including the tips of both the long and short arms, that are not inactivated. 

Nevertheless, the inactivated vaccine approach suffers from several shortcomings. The process could inactivate not only the organism but also destroy the antigen conformation required to elicit protective immunity. Incomplete inactivation (e.g., virion aggregation resulting in poor exposure to the inactivating agent) could result in disease transmission or severe complica-... 

Brown, E, Review of accidents caused by incomplete inactivation of viruses. Dev Biol Stand, 1993. 81 103-7. 

Chemical clastogenesis and mutagenesis both involve a complex series of processes, including pharmacokinetic mechanisms (uptake, transport, diffusion, excretion), metabolic activation and inactivation, production of DNA lesions and their incomplete repair or misrepair, and steps leading to the subsequent expression of mutations in surviving cells or individuals (Thble 7.1). Each of the steps in these processes might conceivably involve first order kinetics at low doses (e.g., diffusion, MichaeUs-Menten enzyme kinetics) and hence be linear. In principle, therefore, the overall process edso might be linear and without threshold. 

The cellular effects of FTase inhibition with 3 were observed with concentrations 5000-50,000 higher than the in vitro IC50 for FTase inhibition by carboxylic acid Id. Incomplete hydrolysis of the lactone in vivo could be partially responsible for this discrepancy in activity. However, it was also found that the lactone prodrug used in the context of the doubly reduced peptide isostere, i.e. 3, was chemically unstable at physiological pH. Rapid cyclization to the diketopiperazine 5 significantly reduced FTase inhibitory activity.40 Simple N-alkylation of the reactive secondary amine to give 4 led to loss of activity vs. FTase. To simultaneously protect the compound from both metabolic inactivation (via peptidases) and chemical instability, isosteric replacements of the second amide bond other than methylene-amino were explored. Since the second amide bond in the tetrapeptide inhibitors could be reduced without loss of activity in vitro, peptide bond replacements which were both rigid (olefin) and flexible (alkyl, ether) were synthesized. 

Proper processing of soybeans requires precise control of moisture content, temperature and processing time. Adequate moisture during processing ensures destruction of the ANFs. Both over- and undertoasting of soybean meal can result in a meal of lower nutritional quality. Underheating produces incomplete inactivation of the ANFs and overtoasting can reduce AA availability. 

Zhou ZH, Unlap T, Li L, Ma HP (2002) Incomplete inactivation of voltage-dependent K+ channels in human B lymphoma cells. J Membr Biol 188 97-105... 

We have developed new reaction systems based on colloidal dispersions [23, 24], namely highly concentrated water-in-oil (gel) emulsions, which could overcome most of the disadvantages of the aqueoussolvent mixtures such as inactivation of the aldolase and incomplete aldehyde solubilization in the medium. These emulsions are characterized by volume fractions of dispersed phase higher than 0.73 [25] therefore, the droplets are deformed and/or polydisperse, separated by a thin film of continuous phase. Water-in-oil gel emulsions of water/Ci4E4/oil 90/4/6 wt%, where C14E4 is a technical grade poly(oxyethylene) tetradecyl ether surfactant, with an average of four moles of ethylene oxide per surfactant molecule and oil can be octane, decane, dodecane, tetradecane, hexadecane, or squalane, were typically chosen as reaction media [23, 26]. 

Disposition in the Body. Incompletely and variably absorbed after oral administration. Rapidly activated by intracellular conversion to thioguanylic acid. Inactivated by methylation to aminomethylthiopurine and by deamination to thioxanthine. About 40% of an oral dose is excreted in the urine as metabolites in 24 hours only traces of thioguanine have been detected. 

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