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41.
Traditionally, peptide drugs are prepared as sterile solutions and administered to patients by daily injection. However, this form of drug delivery causes pain and inconvenience to patients and thus has been poorly accepted. In addition to improving patient compliance, many novel delivery systems have been developed to address the need for prolonged, localized (targeted), or pulsatile drug action. Examples include, but are not limited to oral, nasal, or long-acting controlled release injectable dosage forms; a number of them have been approved by FDA recently. The unique characteristics and the relevant regulatory issues with respect to each type of delivery system are presented. 相似文献
42.
Substance P (SP), one of the established neurotransmitters, evokes an immunoinflammatory response involving leukocyte adhesion to venular endothelium and the degranulation of mast cells. The pathogenetic relationship between these responses, however, remains unresolved. In this study, we propose to examine the changes associated with the activation of mast cells, as well as leukocyte adhesion to venular endothelium by in vivo observation of the rat mesentery. The use of an in vitro assay for intracellular Ca2+ mobilization and the degranulation of mast cells demonstrated the significant upper shift of concentration response to SP (10(-4)-10(-5) M). In vivo experiments on the mesenteric microcirculation also showed that SP induced a significant increase in the number of degranulated mast cells as well as in the number of leukocytes adherent to the venular wall. Tranilast, a mast cell stabilizer, as well as SP antagonist (CP-96,345) significantly attenuated the extent of mast cell degranulation and leukocyte adhesion elicited by SP. Although an immunoneutralization against CD18 by WT-3 significantly attenuated the leukocyte adhesion, it had no influence on the mast cell degranulation after SP superfusion. These separate in vivo observations show that SP induces leukocyte adhesion to the venular endothelium, possibly through the degranulation of mast cells. 相似文献
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AIM: Falling is a serious medical problem for elderly persons. This study was done to look at prevalence and risk factors for falls in community dwelling elderly in Singapore. METHOD: A random sample of 3,000 persons aged 60 years and above was chosen from a database based on the 1990 population census. Letters were sent out to 2,582 subjects who had local and complete addresses. In the letter, they were informed about the purpose of the survey, and invited to participate in a questionnaire and clinical health screening at an appointed date at a polyclinic. Participants were reminded the day before their appointment by telephone, and a new appointment could be given at the subject's convenience. RESULTS: We found a prevalence rate of falls of 17.2%. Two-thirds of these had single falls, while one-third had recurrent falls, defined as having more than one fall within the previous one year. The following factors were found to be significantly associated with increase falling in the elderly: age > or = 75 years (O.R. = 1.82, 95% C.I. 0.95-3.50), female sex (O.R. = 2.5, 95% C.I. 1.40-4.48), Malay race (O.R. = 2.66, 95% C.I. 1.21-5.86), poor vision (O.R. = 1.7, 95% C.I. 0.99-2.90), Barthel's score of less than 20 (O.R. = 1.76, 95% C.I. 0.94-3.28), those taking 2 or more drugs daily (O.R. = 2.1, 95% C.I. 1.22-3.72) and the presence of hypertension (O.R. = 1.78, 95% C.I. 1.06-3.01). Fall rate is also twice as high in women as in men. At the same time, we found that women in the group we studied also tend to exercise less than the men. Fallers also had significantly more mobility and activities of daily living (ADL) disabilities (reflected by a lower Barthel's score) and this is consistent with other results. The only factor that reduced the risk of falling was regular exercise (O.R. = 1.64, 95% C.I. 0.93-2.93). CONCLUSION: In our study, we found differences between the group with single and recurrent falls. In the group with single falls, the fall tend to occur outdoors (O.R. = 2.97, 95% C.I. 1.03-8.60) and during the day (O.R. = 3.47, 95% C.I. 1.20-10.0), tend to be accidental (O.R. = 3.16, 95% C.I. 1.05-9.50) and tend to seek medical attention (O.R. = 3.68, 95% C.I. 1.23-11.0). Overall, 32 persons (46.4%) seek medical treatment after their falls, and of these, 65.6% were women. Risk factors for falls should be screened for all elderly. 相似文献
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YY Xiang DY Wang M Tanaka H Igarashi Y Naito Y Ohtawara Q Shen H Sugimura 《Canadian Metallurgical Quarterly》1996,106(2):271-278
Specific expression of the structure-specific recognition protein (SSRP) gene was investigated in rat fetal, adult, and tumor tissues using a 2.0-kb partial sequence of rat SSRP cDNA isolated from a cDNA library of rat renal cell carcinoma. The results revealed that it was rather specifically expressed in rat fetal kidney and renal cell carcinoma induced by Fenitrilotriacetate, but not in adult kidney, when various organs were tested by Northern blot analysis. In situ hybridization further demonstrated that it was located in the neoplastic cells of renal cell carcinoma and in the epithelial cells of fetal kidney but undetectable in any cells of normal adult kidney. These observations seem to imply the involvement of SSRP gene, which is believed to recognize structural alterations of DNA, in kidney development and carcinogenesis of certain types of kidney cancer. 相似文献
45.
HM Mitchell P Hu Y Chi MH Chen YY Li SL Hazell 《Canadian Metallurgical Quarterly》1998,114(2):256-261
Ascorbate peroxidase (APX) is a hydrogen peroxide-scavenging peroxidase which uses ascorbate (AsA) as the specific electron donor. APX has not been isolated in mammals. Ocular tissue contains AsA at high concentrations, and we detected APX activity in bovine retinal pigment epithelium (RPE) and choroid. We purified APX from bovine RPE and choroid by four chromatographic steps. The purified APX was a monomeric hemoprotein with a molecular mass of 43 kDa. The amino acid sequence of the amino-terminal region of the purified APX showed a high degree of homology to that of plants. The primary product of the APX reaction was identified as the monodehydroascorbate radical. The APX showed high specificity for AsA as an electron donor. This is the first isolation and characterization of APX from mammals, and its role in the protection against active species of oxygen in ocular tissue is discussed. 相似文献
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The effects of glutamate on cultured cortical neurons and the protective effect of ketamine and nifedipine were studied. On day 10 after plating of the cortical cells from 16-18 day-old fetal rats, the cultures were exposed to 50 mumol.L-1 glutamate and low glucose (1 g.L-1) for 10 min-24 h. The results showed that a release of lactate dehydrogenase (LDH) into the culture supernatant was observed as a function of time. The values of LDH efflux in culture medium was significantly lower than those of controls when the cells were pretreated with ketamine or nifedipine 10 min prior to addition of glutamate. More significant decrease of LDH activity in culture medium was observed when the two drugs were used in combination. These results demonstrate that the dissociated cultured cortical neurons from fetal rat are seriously damaged by glutamate. Such damage could be attenuated by ketamine and nifedipine, suggesting that ketamine and nifedipine may protect neurons from the glutamate toxicity, and the effect of combining ketamine and nifedipine was greater than either ketamine or nifedipine alone. 相似文献
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