Plasma augmented

The aqueous in vivo environment for UHMWPE components is in many ways more complex than the gaseous environment to which they are exposed during manufacture, sterilization, and shelf aging. For example, the joint fluid of the hip and knee contains filtered plasma augmented by biomolecules, such as lubricious proteins, that are produced by the synovial membrane [1, 2]. The synovial fluid of patients with arthritis is also known to contain to dissolved oxygen... 

Plasma, augmented A plasma, the electron density of which has been increased by the addition of electrons from an external electron source such as a hollow cathode. 

One function of HK is to present the substrates of factor Xlla in a conformation that facilitates their activation [25, 26]. More difficult to explain is the effect of HK on the rate of factor XII activation in plasma since HK does not interact with factor XII, nor does it augment the activity of kaiiikrein. This effect seems to be largely indirect. First, HK is required for efficient formation of kaiiikrein in surface-activated plasma [26, 27]. Second, since kaiiikrein can disassociate from surface-bound... 

Capacitative Ca2+ entry is the predominant mode of regulated Ca2+ entry in nonexcitable cells but it also occurs in a number of excitable cell types. This pathway of Ca2+ entry is usually associated with the activation of phospholipase C, which mediates the formation of IP3 (see Ch. 20). Intracellular application of IP3 mimics the ability of hormones and neurotransmitters to activate calcium ion entry, and activation of calcium ion entry by hormones and neurotransmitters can be blocked by intracellular application of low-molecular-weight heparin, which potently antagonizes IP3 binding to its receptor. There is considerable evidence for the presence of an IP3 receptor in the plasma membrane of some cells types. 1(1,3,4,5)P4, a product of IP3 phosphorylation, has been shown in some cells to augment this action of IP3 in activating PM calcium ion entry, but in others IP3 alone is clearly sufficient. 

However, the current view of the regulation of calcium ion entry into the cytoplasm by PLC-linked stimuli holds that activation occurs not as a direct result of the action of IP3 on the plasma membrane but indirectly, as a result of depletion of calcium ions from an intracellular store by IP3 [14]. In the context of this capacitative model , the actions of intracellularly applied IP3 and heparin reflect the effects of these maneuvers on intracellular release process from ER into cytosol, rather than via the plasma membrane. The reported actions of I(1,3,4,5)P4, if in fact they do represent physiological control mechanisms, may reflect an ability of I(1,3,4,5)P4 to augment the calcium-releasing ability of IP3, rather than a distinct and... 

The prevalence of concurrent prescriptions raises concern regarding drug interactions with stimulants. Stimulants, especially MPH, have been used to augment the effects of tricyclic antidepressants in the treatment of refractory depression. Although one early report claimed that circulating levels of imipramine can rise seven fold when taken concurrently with MPH (Wharton et al., 1971), a more recent study found that combining stimulants with desipramine (DMI) did not increase the plasma level of DMI relative to children treated with DMI alone (Cohen et al., 1999). 

A normal response is an increase in plasma TSH of 5 to 15 pU/mL above baseline. A response of less than 5 pU/mL above baseline is generally considered to be blunted (some laboratories consider a response below 7 pU/mL to be blunted) and may be consistent with a major depression. An abnormal test is found in approximately 25% of patients with depression. A blunted TSH response (especially in conjunction with an abnormal DST) may help in confirming the differential diagnosis of a major depressive episode and support continued antidepressant treatment. An increased baseline TSH or an augmented TSH response (higher than 30 pU/mL), in conjunction with other thyroid indices, might identify patients with hypothyroidism, mimicking a depressive disorder. These patients may benefit most from thyroid replacement therapy. 

Case Example Because of a patient s partial response to 5 months of clozapine therapy at 600 mg/day, risperidone was added for augmentation (started with 0.5 mg b.i.d. and increased to 1 mg b.i.d. after 1 week). Before this addition, the clozapine plasma level was 344 ng/mL, but after 2 weeks of risperidone augmentation, the level was elevated to 598 ng/mL with no adverse effects and substantial clinical benefit. In another report, there was an increase in the steady-state plasma levels of clozapine (675 mg/day) and its active metabolite norclozapine after the addition of risperidone 2 mg/day in a patient treated for 2 years. Before the addition of risperidone, her clozapine and norclozapine levels were 829 and 1,384 ng/mL, respectively. Two days after risperidone was added, these levels rose to 980 and 1,800 ng/mL. Clozapine dosage was reduced to 500 mg/day, and after 5 days of combined treatment with 4 mg/day of risperidone, the clozapine and norclozapine levels were 110 and 760 ng/mL, respectively. Aside from some mild oculogyric crises, she had no symptoms of clozapine toxicity or clinical changes during the period of cross-tapering. In another case, risperidone was added to clozapine because the patient had relapsed after discontinuation of fluphenazine and had not responded to clozapine. The addition of risperidone resulted in an acute remission of psychosis ( 100). 

In partially responsive or nonresponsive patients, the first issue is to determine whether an individual is truly treatment-resistant, because many receive nontherapeutic doses and the potential for improvement may not be adequately tested. Thus, in some situations, more aggressive treatment (dose increase, augmentation) may be appropriate, if not precluded by adverse effects. In selected cases, it may also be helpful to monitor plasma levels to ensure that they are in a reasonable range (see Pharmacokinetics/Plasma Levels earlier in this chapter). If a patient continues to demonstrate significant symptoms after a sufficient trial (2 to 3 weeks), alternatives to switching to another antipsychotic may include the addition of lithium, an anticonvulsant, or a second antipsychotic agent. An antidepressant or anxiolytic may also be helpful, especially if affective or anxiety symptoms are prominent. 

Plasma levels are in the usual optimal range, but there is insufficient clinical response try another agent, an augmentation strategy, or ECT (see also Alternative Treatment Strategies later in this chapter). 

Pharmacokinetic interactions occur when one drug interferes with the absorption, distribution, metabolism, or excretion of another drug so as to increase or decrease the concentration of free drug in the plasma (and at its site of action). Such interference may be two-way and may involve more than one mechanism. These may augment or counteract each other. 

As the urinary excretion of uric acid increases, the size of the urate pool decreases, although the plasma concentration may not be greatly reduced. In patients who respond favorably, tophaceous deposits of urate are reabsorbed, with relief of arthritis and remineralization of bone. With the ensuing increase in uric acid excretion, a predisposition to the formation of renal stones is augmented rather than decreased therefore, the urine volume should be maintained at a high level, and at least early in treatment the urine pH should be kept above 6.0 by the... 

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