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et al (2006) Perivascular adipose tissue and mesenteric vascular function in spontaneously hypertensive rats Arteriosclerosis, Thrombosis, and Vascular Biology, 26, 1297 302 Gami, AS, Hodge, DO, Herges, RM et al (2007) Obstructive sleep apnea, obesity, and the risk of incident atrial brillation Journal of the American College of Cardiology, 49, 565 71 Gao, YJ, Takemori, K, Su, LY et al (2006) Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion Cardiovascular Research, 71, 363 73 Gao, YJ, Zeng, ZH, Teoh, K et al (2005) Perivascular adipose tissue modulates vascular function in the human internal thoracic artery The Journal of Thoracic and Cardiovascular Surgery, 130, 1130 6 Gardin, JM, McClelland, R, Kitzman, D et al.

gB (cm/GW) 12 11 8.6 10 14 3.8 4.8 3.1 13.7 12 18.0 16.6 12.6 12.6 6.8 18 6.2 130 20 6 6.5 4.5 5

Viewing and Managing Digital Picture Libraries . . . 251 Creating Slideshows Using My Pictures . . . . . . . . . 267 Playing Home Movies with My Video . . . . . . . . . . . 273

(2001) M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study) The American Journal of Cardiology, 87, 1051 7..

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_ where Rnr is the neutron removal cross-section and D0 is the dose equivalent rate per unit neutron fluence rate; i.e., mrem/h per neutron/cm2 s for neutrons of the

4. Choose View Hide to see the final result. 5. Save your drawing. It should look like Figure 23-9.

Semisolid and Solid Dosage Forms Whether the oxidative degradation process is by auto-oxidation (an uncatalyzed reaction which proceeds slowly under the in uence of molecular oxygen) or by chain processes which involve initiation, propagation, and termination reactions, molecular oxygen is very important Consequently, every effort should be made to determine and control oxygen concentration in an aqueous solution Florence and Attwood [9] have given an oxidation scheme involving a chain reaction The description of the scheme is in order to provide an appreciation of the in uence of the interaction of molecular oxygen, components of the solution and even leachables from the packaging materials on oxidation It is believed that initiation can take place through the free radicals formed by organic compounds consequent upon the action of light, heat, or transition metals (eg, copper and iron) present in trace amounts in the buffer.

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The free radicals readily combine with molecular oxygen in the propagation step to form a peroxy radical which then abstracts hydrogen from a molecule of organic compound to form a hydroperoxide and then create another free radical The termination occurs when the free radicals are destroyed by inhibitors or by side reactions which break the chain The presence of certain functional groups is known to make some drugs highly susceptible to oxidative degradation [7, 9] The phenol functional group present in steroids is sensitive to oxidation The ether group is susceptible to oxidation as reported for econazole nitrate and miconazole nitrate Catecholamines such as dopamine and isoproterenol are susceptible to oxidation Phenothiaxines possess a thioether functional group which is oxidized to sulfoxide in the presence of water Many drug molecules possess carbon carbon double bonds which can be easily attacked by peroxyl radicals, leading to oxidative degradation.

In fact, the double bond is highly susceptible to singlet oxygen (which is highly oxidizing); the singlet oxygen is believed to form from the ground state of oxygen called triplet oxygen when excited by light Consequently, the general term oxidation is more than mere exposure of a susceptible drug molecule to oxygen but also exposure to conditions that favor oxidation such as photolysis [6] Amphotericin is a polyene antibiotic with seven conjugated double bonds It is oxidized by peroxy radicals with a loss of activity and aggregation [25] Addition of peroxyl radicals to simvastatin can result in oxidation with the formation of polymeric peroxides [26] Carboxylic acid is another group highly susceptible to oxidation: The rate of oxidation of ascorbic acid depends on oxygen concentration [27] Literature on pharmaceutical sciences is replete with oxidative degradation of drugs in solution.

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5-Aminosalicylic acid undergoes oxidation and the product of oxidation forms polymeric compounds [28] Further, morphine has been reported to be oxidatively degraded in solution [29] as well as hydrocortisone [30]..

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