Elimination of serum

The many different rationales behind growing cells in serum-free media can be divided into three categories  

There are several approaches to the elimination of serum. The approach, or combination of approaches, used should be determined by the goals of the work. 

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Traditionally, the production of mAbs uses complex culture media containing glucose and amino acids as the main sources of carbon for cell metabolism, as well as vitamins, micronutrients and sometimes animal serum, usually fetal bovine serum. Chapter 5 provides a discussion on composition of culture media and recent trends in the search for formulas that do not require the use of animal serum, or of proteins of animal origin. These serum-free formulations use substitutes such as peptones, epithelial and fibroblast growth factors, hydrolysates, yeast extract, choline, and inositol. For the production of mAbs, various serum-free formulas are available, some of these developed specifically for a given cell line (Chu and Robinson, 2001). The development of those media is easier for non-anchorage-dependent cells, such as those used for mAb production. Thus, approximately 50% of the antibodies for therapeutic use are already produced using serum-free media. In some circumstances, the elimination of serum should be accompanied by the addition of other substances with the same shear stress protective effect of serum proteins,... 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctonate in retired fluorochemical production workers. Environ Health Perspect 155 1298-1305... 

The presence of serum-binding proteins. Some biopharmaceuticals (including insulin-like growth factor (IGF), GH and certain cytokines) are notable in that the blood contains proteins that specifically bind them. Such binding proteins can function naturally as transporters or activators, and binding can affect characteristics such as serum elimination rates. 

In a study with human subjects, whose urine pH was controlled with sodium bicarbonate and ammonium chloride, it was found that 10-25% of the administered pseudoephedrine hydrochloride was metabolized to norpseudoephedrine and the elimination of pseudoephedrine and norpseudoephedrine was related to urine pH. As the urine pH increased, the serum half-life of pseudoephedrine and norpseudoephedrine increased.15 In another similar study it was found that a decrease... 

Rats pretreated with xylene or phenobarbital and then exposed to -hexane by inhalation exhibited a markedly increased peak serum concentration of 2,5-hexanedione (Toftgard et al. 1983). Peak serum concentrations were approximately 4 g/mL in control rats, 11 g/mL in xylene-induced rats, and 13 g/mL in phenobarbital-induced rats. Peaks were reached in 1-2 hours. The half-life for elimination from serum was approximately one hour for both pretreated and untreated rats. The high serum 2,5-hexanedione concentrations were correlated with an induction of liver microsomal P-450 content (0.56 nmol/mg protein in control rats, 1.03 nmol/mg in xylene-induced rats, and 1.7 nmol/mg protein in phenobarbital-induced rats, respectively). 

Creatinine is a metabolic breakdown product of muscle and usually has a constant value in an individual. Its value ranges from 0.6 mg/100 mL of serum to 1.2 mg/100 mL of serum. Creatinine is almost exclusively eliminated by the kidneys. Therefore, if the level of creatinine increases in the serum, it is likely that the capability of kidneys to eliminate the drugs is reduced. As a general rule, if the serum creatinine level (Ccr) is doubled, the kidney function is one-half. If the Ccr is quadrupled, the renal (kidney) function is one-fourth or 25%. 

Nitrophenol is colourless, whereas the phenolate ion under basic conditions is yellow in appeanace. Therefore, the elimination of interference due to coloured drugs present in the serum is accomplished effectively by first, measuring the absorbance of the serum under basic conditions, and secondly, under acidic conditions. Thus we have ... 

Hepatic metabolism and excretion in the bile play major roles in the elimination of both vinblastine and vincristine in humans (52) small amounts of vincristine and vinblastine, of the order of 10% of the administered dose, are excreted unchanged in urine. Renal clearance of vinblastine has been reported to be less than 10% of total serum clearance 53). Vinblastine has been reported to inhibit a polymorphic cytochrome P-450 system in human hepatic microsomes, but the concentrations required were much higher than those observed in clinical settings (54). 

The CSF/serum ratio of IgG eliminates the individual variation of serum IgG. The quotient of IgG (CSF/serum) to albumin (CSF/serum) eliminates the variation of the IgG quotient by the individual blood-CSF barrier function. Intrathecal IgG is total CSF IgG minus transudative IgG. The first formulas were based on a linear relationship between Q ib and Qigo (Cl, K3, LI, S4). More recent formulas make use of a hyperbolic or exponential function. The application of the latter two formulas reduces the number of false-positive results in the cases of blood-brain barrier disturbances, while sensitivity is maintained. Soeverijn compared Reiber s hyperbolic formula to five other formulas and showed that Reiber s formula produced the best agreement with the lEF gold standard (LI). For the latest modification of the IgG, IgA, and IgM subclasses of immunoglobulins, see Section 3.2.3. 

An instructive example is the physiological variable serum creatinine. Creatinine is an endogenous metabolite formed from, and thus reflecting, muscle mass. Total body muscle mass is sufficiently constant to render measurement of serum creatinine useful for assessing actual renal function. The serum value of creatinine (R) is namely dependent on the continuous (zero-order) input of creatinine into the blood (A in) and its renal elimination rate, which is a first-order rate process (A out x ) In case of an extensive muscle breakdown, kin will temporarily increase. It may also be permanently low, for example in old age when muscle mass is reduced. Likewise, creatinine clearance may decrease for various reasons, described by a decrease in A out- An increase in creatinine clearance may occur as well, for example following recovery from renal disease. According to pharmacodynamic indirect response models. 

Amiodarone increases the hypoprothrombinemic response to warfarin (an oral anticoagulant) by reducing its metabolism. Patients receiving digoxin may undergo an increase in serum digoxin concentrations when amiodarone is added to the treatment regimen. Amiodarone interferes with hepatic and renal elimination of flecainide, phenytoin, and quinidine. 

The thiazides have a variable effect on elimination of uric acid, which also is secreted by the renal acid secretory mechanism. Administration of thiazide diuretics, especially at low doses, may elevate serum uric acid levels and cause goutlike symptoms. Following large doses, thiazides may compete with uric acid for active reabsorption and thereby may promote uric acid elimination rather than impair it (see Chapter 37). 

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