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1.
Pharmacokinetics of two alternative dosage forms for cyclosporine: liposomes and intralipid 总被引:2,自引:0,他引:2
Cyclosporine (CsA), commercially available as iv or oral Sandimmune, is a potent immunosuppressant which can induce dose-related nephrotoxocity. In addition, the iv product contains a solubilizing agent, Cremophore EL, which in itself is reported to be nephrotoxic and can induce, in sensitized patients, anaphylactic reactions. Solubilization of CsA with liposomes or lipid emulsions could provide a suitable alternative dosage form for iv administration. With this in mind, male New Zealand white rabbits were given iv CsA (10 mg/kg) in three different dosage forms: (1) CsA:liposomes; (2) CsA:Intralipid (soybean oil and phospholipids); and (3) the commercially available Sandimmune (cyclosporine). The CsA concentration in whole blood samples was analyzed by HPLC. The terminal disposition half-life of CsA (t1/2 beta) ranged from 400 to 475 min and was not statistically different among the three groups. However, the distribution characteristics of CsA changed dramatically depending on the dosage form. The volume of distribution of CsA at steady state (Vdss) in Sandimmune was 2.7 +/- 0.2 L/kg and was significantly lower than that of either Intralipid (10.6 +/- 2.7 L/kg) or liposomes (7.4 +/- 2.3 L/kg). A significantly lower total body clearance (TBC) of CsA also was seen for Sandimmune (12.7 +/- 0.3 mL/min/kg) as compared with that of either Intralipid (24.4 +/- 8.2 mL/min/kg) or liposomes (18.9 +/- 3.9 mL/min/kg). Since CsA is extensively bound to lipoproteins, it is surprising that both test vehicles showed a different distribution pattern.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Venkataram M Moosa M Devi L 《Indian journal of dermatology, venereology and leprology》2001,67(6):294-298
Cutaneous leishmaniasis presents a spectrum of manifestations both clinically and histologically. Several previous studies have established the value of histological examination in the diagnosis of cutaneous leishmaniasis. Different reaction patterns have been reported. Forty cases of cutaneous leishmaniasis were studied in the Sultanate of Oman, with particular reference to the different histological features. Clinical features were correlated with the histological patterns. Four histological patterns were identified-1) diffuse macrophage infiltration without necrosis, 2) macrophage infiltration with necrosis. 3) early reactive granuloma and 4) established epitheloid granuloma. LD bodies were identified in 65% of cases. Epidermal features were nonspecific. Though the patterns could be correlated with the duration and the clinical type of lesion in a few cases, the correlation was not consistent. 相似文献
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We have developed a simple, rapid method for analysing faecal iron using a microwave oven for digestion followed by atomic absorption spectrometry. The chelating effect of 1,2-dimethyl-3-hydroxy-pyrid-4-one (DMHP) has been tested in rats with experimental iron overloading and three routes of DHMP administration, oral, subcutaneous, and intraperitoneal, have been compared. Regardless of the route of administration, we have found that DMHP promotes iron excretion via the urine. We have not observed a difference in the amount of iron excreted in the faeces before and after DMHP administration by any route. The subcutaneous route of administration is the most effective in promoting iron excretion, followed by the intraperitoneal route. Although most convenient for clinical use, oral administration promotes the excretion of only a small fraction of that by the subcutaneous route. 相似文献
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Raveendranathan D Shivakumar V Jayaram N Rao NP Venkatasubramanian G 《Archives of women's mental health》2012,15(2):147-148
The role of estrogens in schizophrenia has been proposed from the observation of schizophrenia occurring later and with symptom
severity being lesser in women. Utility of estrogens in treatment of psychoses, though seen to be useful, comes with inherent
risks of neoplasias, given its agonistic action on breast and endometrium. This risk can be overcome with use of selective
estrogen receptor modulators, like raloxifene. Raloxifene has been used in schizophrenia, with improvement in symptoms and
cognitive functions. We report the use of raloxifene as an adjunctive treatment, with risperidone, in treatment-resistant
form of schizophrenia. The patient, a 29-year-old woman, over a 7-month follow-up period, showed significant improvement in
socio-occupational functioning, with reduction in symptom severity. 相似文献
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Choi JM Hutson AM Estes MK Prasad BV 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(27):9175-9180
Members of Norovirus, a genus in the family Caliciviridae, are causative agents of epidemic diarrhea in humans. Susceptibility to several noroviruses is linked to human histo-blood type, and its determinant histo-blood group antigens (HBGAs) are regarded as receptors for these viruses. Specificity for these carbohydrates is strain-dependent. Norwalk virus (NV) is the prototype genogroup I norovirus that specifically recognizes A- and H-type HBGA, in contrast to genogroup II noroviruses that exhibit a more diverse HBGA binding pattern. To understand the structural basis for how HBGAs interact with the NV capsid protein, and how the specificity is achieved, we carried out x-ray crystallographic analysis of the capsid protein domain by itself and in complex with A- and H-type HBGA at a resolution of approximately 1.4 A. Despite differences in their carbohydrate sequence and linkage, both HBGAs bind to the same surface-exposed site in the capsid protein and project outward from the capsid surface, substantiating their possible role in initiating cell attachment. Precisely juxtaposed polar side chains that engage the sugar hydroxyls in a cooperative hydrogen bonding and a His/Trp pair involved in a cation-pi interaction contribute to selective and specific recognition of A- and H-type HBGAs. This unique binding epitope, confirmed by mutational analysis, is highly conserved, but only in the genogroup I noroviruses, suggesting that a mechanism by which noroviruses infect broader human populations is by evolving different sites with altered HBGA specificities. 相似文献