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    By denaturing leucine aminopeptidase and preventing enzyme-substrate complex formation discount 5mg compazine mastercard, the bile salt sodium glycocholate has been shown to protect insulin from proteolysis in the rat nasal mucosa buy compazine 5mg line. In addition to formulation additives buy 5mg compazine visa, peptides can be chemically modified to improve their stability to proteases, as described in Chapter 1 (Section 1. However, altering the tonicity of the formulation had no effect on the absorption of human granulocyte colony-stimulating factor (molecular weight 19 kDa). In another study, decreasing the pH of the formulation was shown to enhance absorption. Alterations of osmotic pressure and pH beyond a certain range might be expected to result in damage to the epithelium and hence increase its permeability to xenobiotics. Delivering the drug as a dry powder 243 A further approach has been to deliver drugs in the form of a powder (but without a bioadhesive carrier). For example, freeze-dried insulin has been shown to be better absorbed as a powder than in solution, although the absorption of glucagon and dihydroergotamine, when delivered from liquid or powder formulations, was equivalent. However, problems which require resolving include developing absorption promoters with minimal toxicity and overcoming adverse nasal pathology to ensure accurate and reproducible dosing. List the mechanisms by which the permeability of the nasal epithelium may be increased to improve the efficacy of nasal drug delivery. Delivery of anti-asthmatic and other locally acting drugs directly 245 to their site of action reduces the dose needed to produce a pharmacological effect, while the low concentrations in the systemic circulation may also reduce side-effects. The lung may additionally be employed as a route for delivery of drugs into the systemic circulation, and onward to an effect site located elsewhere in the body. A product containing ergotamine tartrate is available as an aerosolized dosage inhaler for the treatment of migraine. Volatile anesthetics, including, for example, halothane, are also given via the pulmonary route. In recent years, the possibility of utilizing the pulmonary route for the systemic delivery of peptides and other molecules which are not absorbed through the gastrointestinal tract has also been explored. Pulmonary drug delivery for both local and systemic effects will be discussed in this chapter. There are a number of schemes for categorizing the different regions of the respiratory tract. With respect to pulmonary drug delivery, division into the following three regions is useful (Figure 10. Every branching of the tracheobronchial tree leads to a new “generation” of airways; for example, the trachea (“generation 0”) bifurcates into two main bronchi (“generation 1”) and then follows sequential branching into lobar bronchi (“generation 2”), segmental bronchi (“generation 3”), intrasegmental bronchi, bronchioles, secondary bronchioles and ultimately the terminal bronchioles (“generation 16”). The terminal bronchioles mark the limit of the tracheobronchial region, beyond which lies the alveolar region (“generations 17 to 23”). Progression from the trachea to the extremities of the tracheobronchial tree is characterized by decreases in both the diameter and length of the tubules with each branching, but the geometrically increasing number of airways results in dramatic increases in surface area. It should be borne in mind, however, that in humans, the left and right lungs are not identical and each contains irregular dichotomous and trichotomous branching patterns. Additionally, while the average path length from trachea to terminal bronchioles is 16 branches, short paths of only 8 to 10 branches may also exist. The alveolar region begins at the respiratory bronchioles, where alveoli begin to appear in the airway walls. Further branching of the respiratory bronchioles is associated with increasing frequency of alveoli appearing until the airway terminates at a respiratory unit, which contains alveolar ducts, atria and about 20 alveoli. The alveoli are packed tightly with adjacent alveoli separated by a common alveolar septum. The diversity of pulmonary epithelia can be illustrated by examining its structure at three principal levels (Figure 10.

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    In the partner condition compazine 5mg line, the medium and low groups conformed more than the high group (see above) compazine 5 mg online. Samelson (115) reports in an abstract that he failed to find a relationship between need affiliation and conformity on a discrimination task discount compazine 5 mg. Moeller and Applezweig (102) placed women college students into groups representing combinations of high and low social and selfapproval needs, as measured by a sentence completion form of The Behavior Interpretation Inventory. No differences were found for persons scoring high in self-approval needs and low in social approval needs, or for those scoring high on both measures. Krebs (80) validated the hypothesis that the greater the achievement need of a person, the more resistant he is to opinion change. Samelson (115) provided information that might allow the individual to account for the discrepancy between physical and social reality. Significantly less conformity was found under the reduced conflict situation when prior failure by the others provided the naive subject with an "explanation" for the social discrepancy. In the usual full conflict situation, both need achievement and social -256- approach were negatively but not significantly correlated with conformity, whereas under the reduced conflict condition the correlation was positive and significant. Since only one or two studies have employed the same measures of strength of needs, the conclusions drawn can only be regarded as tentative ones. In self-ratings on the Gough Adjective Check List, subjects low in conformity perceived themselves as possessing intellectual and cognitive originality, open-mindedness, a high degree of personal involvement, emotional reactivity, and lack of social ease or absence of social virtues; yielders perceived themselves as possessing ease and facility in interpersonal relations, personal effectiveness, playfulness in achieving goals, and personal stability and health. On the eighty-four descriptive item check list, independents placed significantly higher values on creativity, close interpersonal relations, and the importance of the individual as opposed to the group. Yielders saw themselves as practical-minded, physicalistic in thinking, and group-oriented. Self-descriptive questionnaire and personality inventories, used by Crutchfield (34) to contrast extreme groups, characterized the independent person as one who is adventurous, self-assertive, possessed of self-respect, and free from compulsion about rules. Conforming persons were seen as rigid, externally sanctioned, inconsistent, anxious, and possessing moralistic attitudes and conventionality of values. In another study by Crutchfield (33), staff ratings on an adjective check list described those subjects most responsive to social influence as fluid, impulsive, tense, and disturbed; those least responsive as rigid, calm, conventional, and practical; those intermediate in responsiveness as moderate, conventional, careful, stable, quiet, intelligent, and serious. On self-ratings, those who were most responsive agreed with the staff assessment; those least responsive tended to overrate themselves; whereas those who were intermediately responsive underrated themselves. Crutchfield (32) also reports significant relationships between responsiveness and such variables as impulsiveness, dominance, flexibility, spontaneity, femininity, and independence of judgmemt, as well as differences between groups in self-perception based on results from adjective check lists. In a study utilizing "normal" subjects, Cervin (27) selected as subjects high and low scorers on several pencil and paper tests of emotional stability. Highly unstable subjects were found to be significantly more likely to change their opinions under opposition. Levine, Laffal, Berkowitz, Lindemann, and Drevdahl (84) contrasted the variability in individual scores on the autokinetic task for patients in a Veterans Administration hospital. The psychiatric group was found to be more variable in perceptual judgments and to show less convergence toward group norms than the "control" group. Didato (36) obtained similar results for schizophrenic compared with normal subjects. Degree of regression in chronic schizophrenia has been reported by Spohn (125) to be related to the tendency to modify judgments in accordance with group norms, with those patients rated as moderately regressed showing more conformity in perceptual judgments than those rated as markedly regressed. Blake, Helson, and Mouton (18) investigated the generality issue for responses to various tasks under simulated group conditions. Generality of susceptibility was demonstrated by individual consistency for all tasks.

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